Epigenetic control of pancreatic cancer metastasis

1.

Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA: a Cancer Journal for Clinicians, 73(1), 17–48. https://doi.org/10.3322/caac.21763CrossRefPubMed

2.

Park, W., Chawla, A., & O'Reilly, E. M. (2021). Pancreatic cancer: A review. JAMA, 326(9), 851–862. https://doi.org/10.1001/jama.2021.13027CrossRefPubMedPubMedCentral

3.

Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023). Pancreatic cancer: Advances and challenges. Cell, 186(8), 1729–1754. https://doi.org/10.1016/j.cell.2023.02.014CrossRefPubMed

4.

Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., Leach, S. D., & Stanger, B. Z. (2012). EMT and dissemination precede pancreatic tumor formation. Cell, 148(1-2), 349–361. https://doi.org/10.1016/j.cell.2011.11.025CrossRefPubMedPubMedCentral

5.

Haeno, H., Gonen, M., Davis, M. B., Herman, J. M., Iacobuzio-Donahue, C. A., & Michor, F. (2012). Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. Cell, 148(1-2), 362–375. https://doi.org/10.1016/j.cell.2011.11.060CrossRefPubMedPubMedCentral

6.

Waddell, N., Pajic, M., Patch, A. M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., Quek, K., Quinn, M. C., Robertson, A. J., Fadlullah, M. Z., Bruxner, T. J., Christ, A. N., Harliwong, I., Idrisoglu, S., Manning, S., Nourse, C., & Grimmond, S. M. (2015). Whole genomes redefine the mutational landscape of pancreatic cancer. Nature, 518(7540), 495–501. https://doi.org/10.1038/nature14169CrossRefPubMedPubMedCentral

7.

Nguyen, B., Fong, C., Luthra, A., Smith, S. A., DiNatale, R. G., Nandakumar, S., Walch, H., Chatila, W. K., Madupuri, R., Kundra, R., Bielski, C. M., Mastrogiacomo, B., Donoghue, M. T. A., Boire, A., Chandarlapaty, S., Ganesh, K., Harding, J. J., Iacobuzio-Donahue, C. A., Razavi, P., & Schultz, N. (2022). Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell, 185(3), 563–575 e511. https://doi.org/10.1016/j.cell.2022.01.003CrossRefPubMedPubMedCentral

8.

Connor, A. A., Denroche, R. E., Jang, G. H., Lemire, M., Zhang, A., Chan-Seng-Yue, M., Wilson, G., Grant, R. C., Merico, D., Lungu, I., Bartlett, J. M. S., Chadwick, D., Liang, S. B., Eagles, J., Mbabaali, F., Miller, J. K., Krzyzanowski, P., Armstrong, H., Luo, X., & Gallinger, S. (2019). Integration of genomic and transcriptional features in pancreatic cancer reveals increased cell cycle progression in metastases. Cancer Cell, 35(2), 267–282 e267. https://doi.org/10.1016/j.ccell.2018.12.010CrossRefPubMedPubMedCentral

9.

Makohon-Moore, A. P., Zhang, M., Reiter, J. G., Bozic, I., Allen, B., Kundu, D., Chatterjee, K., Wong, F., Jiao, Y., Kohutek, Z. A., Hong, J., Attiyeh, M., Javier, B., Wood, L. D., Hruban, R. H., Nowak, M. A., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., & Iacobuzio-Donahue, C. A. (2017). Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nature Genetics, 49(3), 358–366. https://doi.org/10.1038/ng.3764CrossRefPubMedPubMedCentral

10.

McDonald, O. G., Li, X., Saunders, T., Tryggvadottir, R., Mentch, S. J., Warmoes, M. O., Word, A. E., Carrer, A., Salz, T. H., Natsume, S., Stauffer, K. M., Makohon-Moore, A., Zhong, Y., Wu, H., Wellen, K. E., Locasale, J. W., Iacobuzio-Donahue, C. A., & Feinberg, A. P. (2017). Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nature Genetics, 49(3), 367–376. https://doi.org/10.1038/ng.3753CrossRefPubMedPubMedCentral

11.

Mueller, S., Engleitner, T., Maresch, R., Zukowska, M., Lange, S., Kaltenbacher, T., Konukiewitz, B., Ollinger, R., Zwiebel, M., Strong, A., Yen, H. Y., Banerjee, R., Louzada, S., Fu, B., Seidler, B., Gotzfried, J., Schuck, K., Hassan, Z., Arbeiter, A., & Rad, R. (2018). Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature, 554(7690), 62–68. https://doi.org/10.1038/nature25459CrossRefPubMedPubMedCentral

12.

Chan-Seng-Yue, M., Kim, J. C., Wilson, G. W., Ng, K., Figueroa, E. F., O'Kane, G. M., Connor, A. A., Denroche, R. E., Grant, R. C., McLeod, J., Wilson, J. M., Jang, G. H., Zhang, A., Dodd, A., Liang, S. B., Borgida, A., Chadwick, D., Kalimuthu, S., Lungu, I., & Notta, F. (2020). Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution. Nature Genetics, 52(2), 231–240. https://doi.org/10.1038/s41588-019-0566-9CrossRefPubMed

13.

Maddipati, R., Norgard, R. J., Baslan, T., Rathi, K. S., Zhang, A., Saeid, A., Higashihara, T., Wu, F., Kumar, A., Annamalai, V., Bhattacharya, S., Raman, P., Adkisson, C. A., Pitarresi, J. R., Wengyn, M. D., Yamazoe, T., Li, J., Balli, D., LaRiviere, M. J., & Stanger, B. Z. (2022). MYC levels regulate metastatic heterogeneity in pancreatic adenocarcinoma. Cancer Discovery, 12(2), 542–561. https://doi.org/10.1158/2159-8290.CD-20-1826CrossRefPubMed

14.

Brar, G., Blais, E. M., Joseph Bender, R., Brody, J. R., Sohal, D., Madhavan, S., Picozzi, V. J., Hendifar, A. E., Chung, V. M., Halverson, D., Mikhail, S., Matrisian, L. M., Rahib, L., Petricoin, E., & Pishvaian, M. J. (2019). Multi-omic molecular comparison of primary versus metastatic pancreatic tumours. British Journal of Cancer, 121(3), 264–270. https://doi.org/10.1038/s41416-019-0507-5CrossRefPubMedPubMedCentral

15.

Burdziak, C., Alonso-Curbelo, D., Walle, T., Reyes, J., Barriga, F. M., Haviv, D., Xie, Y., Zhao, Z., Zhao, C. J., Chen, H. A., Chaudhary, O., Masilionis, I., Choo, Z. N., Gao, V., Luan, W., Wuest, A., Ho, Y. J., Wei, Y., Quail, D. F., & Pe’er, D. (2023). Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis. Science, 380(6645), eadd5327. https://doi.org/10.1126/science.add5327CrossRefPubMedPubMedCentral

16.

Roe, J. S., Hwang, C. I., Somerville, T. D. D., Milazzo, J. P., Lee, E. J., Da Silva, B., Maiorino, L., Tiriac, H., Young, C. M., Miyabayashi, K., Filippini, D., Creighton, B., Burkhart, R. A., Buscaglia, J. M., Kim, E. J., Grem, J. L., Lazenby, A. J., Grunkemeyer, J. A., Hollingsworth, M. A., & Vakoc, C. R. (2017). Enhancer reprogramming promotes pancreatic cancer metastasis. Cell, 170(5), 875–888 e820. https://doi.org/10.1016/j.cell.2017.07.007CrossRefPubMedPubMedCentral

17.

Milan, M., Balestrieri, C., Alfarano, G., Polletti, S., Prosperini, E., Spaggiari, P., Zerbi, A., Diaferia, G. R., & Natoli, G. (2019). FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner. The EMBO Journal, 38(20), e102161. https://doi.org/10.15252/embj.2019102161CrossRefPubMedPubMedCentral

18.

Chiou, S. H., Risca, V. I., Wang, G. X., Yang, D., Gruner, B. M., Kathiria, A. S., Ma, R. K., Vaka, D., Chu, P., Kozak, M., Castellini, L., Graves, E. E., Kim, G. E., Mourrain, P., Koong, A. C., Giaccia, A. J., & Winslow, M. M. (2017). BLIMP1 induces transient metastatic heterogeneity in pancreatic cancer. Cancer Discovery, 7(10), 1184–1199. https://doi.org/10.1158/2159-8290.CD-17-0250CrossRefPubMedPubMedCentral

19.

Whittle, M. C., Izeradjene, K., Rani, P. G., Feng, L., Carlson, M. A., DelGiorno, K. E., Wood, L. D., Goggins, M., Hruban, R. H., Chang, A. E., Calses, P., Thorsen, S. M., & Hingorani, S. R. (2015). RUNX3 controls a metastatic switch in pancreatic ductal adenocarcinoma. Cell, 161(6), 1345–1360. https://doi.org/10.1016/j.cell.2015.04.048CrossRefPubMedPubMedCentral

20.

Krebs, A. M., Mitschke, J., Lasierra Losada, M., Schmalhofer, O., Boerries, M., Busch, H., Boettcher, M., Mougiakakos, D., Reichardt, W., Bronsert, P., Brunton, V. G., Pilarsky, C., Winkler, T. H., Brabletz, S., Stemmler, M. P., & Brabletz, T. (2017). The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nature Cell Biology, 19(5), 518–529. https://doi.org/10.1038/ncb3513CrossRefPubMed

21.

Takano, S., Reichert, M., Bakir, B., Das, K. K., Nishida, T., Miyazaki, M., Heeg, S., Collins, M. A., Marchand, B., Hicks, P. D., Maitra, A., & Rustgi, A. K. (2016). Prrx1 isoform switching regulates pancreatic cancer invasion and metastatic colonization. Genes & Development, 30(2), 233–247. https://doi.org/10.1101/gad.263327.115CrossRef

22.

Dai, C., Rennhack, J. P., Arnoff, T. E., Thaker, M., Younger, S. T., Doench, J. G., Huang, A. Y., Yang, A., Aguirre, A. J., Wang, B., Mun, E., O'Connell, J. T., Huang, Y., Labella, K., Talamas, J. A., Li, J., Ilic, N., Hwang, J., Hong, A. L., & Hahn, W. C. (2021). SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization. Cell Reports, 36(4), 109443. https://doi.org/10.1016/j.celrep.2021.109443CrossRefPubMed

23.

Schneeweis, C., Diersch, S., Hassan, Z., Krauss, L., Schneider, C., Lucarelli, D., Falcomata, C., Steiger, K., Ollinger, R., Kramer, O. H., Arlt, A., Grade, M., Schmidt-Supprian, M., Hessmann, E., Wirth, M., Rad, R., Reichert, M., Saur, D., & Schneider, G. (2022). AP1/Fra1 confers resistance to MAPK cascade inhibition in pancreatic cancer. Cellular and Molecular Life Sciences, 80(1), 12. https://doi.org/10.1007/s00018-022-04638-yCrossRefPubMedPubMedCentral

24.

Hamdan, F. H., & Johnsen, S. A. (2018). DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network. Proceedings of the National Academy of Sciences, 115(52), E12343–E12352. https://doi.org/10.1073/pnas.1812915116CrossRef

25.

Somerville, T. D. D., Xu, Y., Miyabayashi, K., Tiriac, H., Cleary, C. R., Maia-Silva, D., Milazzo, J. P., Tuveson, D. A., & Vakoc, C. R. (2018). TP63-mediated enhancer reprogramming drives the squamous subtype of pancreatic ductal adenocarcinoma. Cell Reports, 25(7), 1741–1755 e1747. https://doi.org/10.1016/j.celrep.2018.10.051CrossRefPubMed

26.

Sahin, I. H., Elias, H., Chou, J. F., Capanu, M., & O’Reilly, E. M. (2018). Pancreatic adenocarcinoma: Insights into patterns of recurrence and disease behavior. BMC Cancer, 18(1), 769. https://doi.org/10.1186/s12885-018-4679-9CrossRefPubMedPubMedCentral

27.

Yachida, S., White, C. M., Naito, Y., Zhong, Y., Brosnan, J. A., Macgregor-Das, A. M., Morgan, R. A., Saunders, T., Laheru, D. A., Herman, J. M., Hruban, R. H., Klein, A. P., Jones, S., Velculescu, V., Wolfgang, C. L., & Iacobuzio-Donahue, C. A. (2012). Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors. Clinical Cancer Research, 18(22), 6339–6347. https://doi.org/10.1158/1078-0432.CCR-12-1215CrossRefPubMedPubMedCentral

28.

Carstens, J. L., Yang, S., Correa de Sampaio, P., Zheng, X., Barua, S., McAndrews, K. M., Rao, A., Burks, J. K., Rhim, A. D., & Kalluri, R. (2021). Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer. Cell Reports, 35(2), 108990. https://doi.org/10.1016/j.celrep.2021.108990CrossRefPubMed

29.

Krauss, L., Urban, B. C., Hastreiter, S., Schneider, C., Wenzel, P., Hassan, Z., Wirth, M., Lankes, K., Terrasi, A., Klement, C., Cernilogar, F. M., Ollinger, R., de Andrade Kratzig, N., Engleitner, T., Schmid, R. M., Steiger, K., Rad, R., Kramer, O. H., Reichert, M., & Schneider, G. (2022). HDAC2 facilitates pancreatic cancer metastasis. Cancer Research, 82(4), 695–707. https://doi.org/10.1158/0008-5472.CAN-20-3209CrossRefPubMed

30.

Cheng, P., Chen, Y., He, T. L., Wang, C., Guo, S. W., Hu, H., Ni, C. M., Jin, G., & Zhang, Y. J. (2019). Menin coordinates C/EBPbeta-mediated TGF-beta signaling for epithelial-mesenchymal transition and growth inhibition in pancreatic cancer. Molecular Therapy--Nucleic Acids, 18, 155–165. https://doi.org/10.1016/j.omtn.2019.08.013CrossRefPubMedPubMedCentral

31.

Chang, C. J., Chao, C. H., Xia, W., Yang, J. Y., Xiong, Y., Li, C. W., Yu, W. H., Rehman, S. K., Hsu, J. L., Lee, H. H., Liu, M., Chen, C. T., Yu, D., & Hung, M. C. (2011). p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nature Cell Biology, 13(3), 317–323. https://doi.org/10.1038/ncb2173CrossRefPubMedPubMedCentral

32.

Aiello, N. M., Maddipati, R., Norgard, R. J., Balli, D., Li, J., Yuan, S., Yamazoe, T., Black, T., Sahmoud, A., Furth, E. E., Bar-Sagi, D., & Stanger, B. Z. (2018). EMT subtype influences epithelial plasticity and mode of cell migration. Developmental Cell, 45(6), 681–695 e684. https://doi.org/10.1016/j.devcel.2018.05.027CrossRefPubMedPubMedCentral

33.

Semaan, A., Bernard, V., Kim, D. U., Lee, J. J., Huang, J., Kamyabi, N., Stephens, B. M., Qiao, W., Varadhachary, G. R., Katz, M. H., Shen, Y., San Lucas, F. A., Gascoyne, P., Alvarez, H. A., Maitra, A., & Guerrero, P. A. (2021). Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer. British Journal of Cancer, 124(12), 1970–1977. https://doi.org/10.1038/s41416-021-01350-9CrossRefPubMedPubMedCentral

34.

Yuan, S., Norgard, R. J., & Stanger, B. Z. (2019). Cellular plasticity in cancer. Cancer Discovery, 9(7), 837–851. https://doi.org/10.1158/2159-8290.CD-19-0015CrossRefPubMedPubMedCentral

35.

Gerstberger, S., Jiang, Q., & Ganesh, K. (2023). Metastasis. Cell, 186(8), 1564–1579. https://doi.org/10.1016/j.cell.2023.03.003CrossRefPubMedPubMedCentral

36.

van Roey, R., Brabletz, T., Stemmler, M. P., & Armstark, I. (2021). Deregulation of transcription factor networks driving cell plasticity and metastasis in pancreatic cancer. Frontiers in Cell and Developmental Biology, 9, 753456. https://doi.org/10.3389/fcell.2021.753456CrossRefPubMedPubMedCentral

37.

Lan, L., Evan, T., Li, H., Hussain, A., Ruiz, E. J., Zaw Thin, M., Ferreira, R. M. M., Ps, H., Riising, E. M., Zen, Y., Almagro, J., Ng, K. W., Soro-Barrio, P., Nelson, J., Koifman, G., Carvalho, J., Nye, E. L., He, Y., Zhang, C., & Behrens, A. (2022). GREM1 is required to maintain cellular heterogeneity in pancreatic cancer. Nature, 607(7917), 163–168. https://doi.org/10.1038/s41586-022-04888-7CrossRefPubMed

38.

Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A. (2018). Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors. Cancer Cell, 33(3), 512–526 e518. https://doi.org/10.1016/j.ccell.2018.02.003CrossRefPubMedPubMedCentral

39.

Patil, S., Forster, T., Reutlinger, K., Kopp, W., Versemann, L., Spitalieri, J., Gaedcke, J., Strobel, P., Singh, S. K., Ellenrieder, V., Neesse, A., & Hessmann, E. (2021). Chromatin-independent interplay of NFATc1 and EZH2 in pancreatic cancer. Cells, 10(12). https://doi.org/10.3390/cells10123463

40.

Lomberk, G., Blum, Y., Nicolle, R., Nair, A., Gaonkar, K. S., Marisa, L., Mathison, A., Sun, Z., Yan, H., Elarouci, N., Armenoult, L., Ayadi, M., Ordog, T., Lee, J. H., Oliver, G., Klee, E., Moutardier, V., Gayet, O., Bian, B., & Urrutia, R. (2018). Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nature Communications, 9(1), 1978. https://doi.org/10.1038/s41467-018-04383-6CrossRefPubMedPubMedCentral

41.

Massague, J., & Ganesh, K. (2021). Metastasis-initiating cells and ecosystems. Cancer Discovery, 11(4), 971–994. https://doi.org/10.1158/2159-8290.CD-21-0010CrossRefPubMedPubMedCentral

42.

Espinet, E., Gu, Z., Imbusch, C. D., Giese, N. A., Buscher, M., Safavi, M., Weisenburger, S., Klein, C., Vogel, V., Falcone, M., Insua-Rodriguez, J., Reitberger, M., Thiel, V., Kossi, S. O., Muckenhuber, A., Sarai, K., Lee, A. Y. L., Backx, E., Zarei, S., & Trumpp, A. (2021). Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin. Cancer Discovery, 11(3), 638–659. https://doi.org/10.1158/2159-8290.CD-20-1202CrossRefPubMed

43.

Feinberg, A. P., & Levchenko, A. (2023). Epigenetics as a mediator of plasticity in cancer. Science, 379(6632), eaaw3835. https://doi.org/10.1126/science.aaw3835CrossRefPubMed

44.

Hamdan, F. H., Abdelrahman, A. M., Kutschat, A. P., Wang, X., Ekstrom, T. L., Jalan-Sakrikar, N., Wegner Wippel, C., Taheri, N., Tamon, L., Kopp, W., Aggrey-Fynn, J., Bhagwate, A. V., Alva-Ruiz, R., Lynch, I., Yonkus, J., Kosinsky, R. L., Gaedcke, J., Hahn, S. A., Siveke, J. T., & Johnsen, S. A. (2023). Interactive enhancer hubs (iHUBs) mediate transcriptional reprogramming and adaptive resistance in pancreatic cancer. Gut, 72(6), 1174–1185. https://doi.org/10.1136/gutjnl-2022-328154CrossRefPubMed

45.

Tie, F., Banerjee, R., Saiakhova, A. R., Howard, B., Monteith, K. E., Scacheri, P. C., Cosgrove, M. S., & Harte, P. J. (2014). Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize polycomb silencing. Development, 141(5), 1129–1139. https://doi.org/10.1242/dev.102392CrossRefPubMedPubMedCentral

46.

Tie, F., Banerjee, R., Stratton, C. A., Prasad-Sinha, J., Stepanik, V., Zlobin, A., Diaz, M. O., Scacheri, P. C., & Harte, P. J. (2009). CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development, 136(18), 3131–3141. https://doi.org/10.1242/dev.037127CrossRefPubMedPubMedCentral

47.

Zhang, T., Cooper, S., & Brockdorff, N. (2015). The interplay of histone modifications - writers that read. EMBO Reports, 16(11), 1467–1481. https://doi.org/10.15252/embr.201540945CrossRefPubMedPubMedCentral

48.

Lee, J. S., Smith, E., & Shilatifard, A. (2010). The language of histone crosstalk. Cell, 142(5), 682–685. https://doi.org/10.1016/j.cell.2010.08.011CrossRefPubMedPubMedCentral

49.

Soares, L. M., He, P. C., Chun, Y., Suh, H., Kim, T., & Buratowski, S. (2017). Determinants of histone H3K4 methylation patterns. Molecular Cell, 68(4), 773–785 e776. https://doi.org/10.1016/j.molcel.2017.10.013CrossRefPubMedPubMedCentral

50.

Zhao, W., Xu, Y., Wang, Y., Gao, D., King, J., Xu, Y., & Liang, F. S. (2021). Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation. Science Reports, 11(1), 15912. https://doi.org/10.1038/s41598-021-95398-5CrossRef

51.

Cai, Y., Zhang, Y., Loh, Y. P., Tng, J. Q., Lim, M. C., Cao, Z., Raju, A., Lieberman Aiden, E., Li, S., Manikandan, L., Tergaonkar, V., Tucker-Kellogg, G., & Fullwood, M. J. (2021). H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. Nature Communications, 12(1), 719. https://doi.org/10.1038/s41467-021-20940-yCrossRefPubMedPubMedCentral

52.

Stathis, A., & Bertoni, F. (2018). BET proteins as targets for anticancer treatment. Cancer Discovery, 8(1), 24–36. https://doi.org/10.1158/2159-8290.CD-17-0605CrossRefPubMed

53.

Belkina, A. C., & Denis, G. V. (2012). BET domain co-regulators in obesity, inflammation and cancer. Nature Reviews Cancer, 12(7), 465–477. https://doi.org/10.1038/nrc3256CrossRefPubMedPubMedCentral

54.

Winter, G. E., Mayer, A., Buckley, D. L., Erb, M. A., Roderick, J. E., Vittori, S., Reyes, J. M., di Iulio, J., Souza, A., Ott, C. J., Roberts, J. M., Zeid, R., Scott, T. G., Paulk, J., Lachance, K., Olson, C. M., Dastjerdi, S., Bauer, S., Lin, C. Y., & Bradner, J. E. (2017). BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitment. Molecular Cell, 67(1), 5–18 e19. https://doi.org/10.1016/j.molcel.2017.06.004CrossRefPubMedPubMedCentral

55.

Jang, M. K., Mochizuki, K., Zhou, M., Jeong, H. S., Brady, J. N., & Ozato, K. (2005). The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Molecular Cell, 19(4), 523–534. https://doi.org/10.1016/j.molcel.2005.06.027CrossRefPubMed

56.

Mazur, P. K., Herner, A., Mello, S. S., Wirth, M., Hausmann, S., Sanchez-Rivera, F. J., Lofgren, S. M., Kuschma, T., Hahn, S. A., Vangala, D., Trajkovic-Arsic, M., Gupta, A., Heid, I., Noel, P. B., Braren, R., Erkan, M., Kleeff, J., Sipos, B., Sayles, L. C., & Siveke, J. T. (2015). Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nature Medicine, 21(10), 1163–1171. https://doi.org/10.1038/nm.3952CrossRefPubMedPubMedCentral

57.

Bian, B., Bigonnet, M., Gayet, O., Loncle, C., Maignan, A., Gilabert, M., Moutardier, V., Garcia, S., Turrini, O., Delpero, J. R., Giovannini, M., Grandval, P., Gasmi, M., Ouaissi, M., Secq, V., Poizat, F., Nicolle, R., Blum, Y., Marisa, L., & Iovanna, J. (2017). Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: Implications for individualized medicine efforts. EMBO Molecular Medicine, 9(4), 482–497. https://doi.org/10.15252/emmm.201606975CrossRefPubMedPubMedCentral

58.

Zanconato, F., Battilana, G., Forcato, M., Filippi, L., Azzolin, L., Manfrin, A., Quaranta, E., Di Biagio, D., Sigismondo, G., Guzzardo, V., Lejeune, P., Haendler, B., Krijgsveld, J., Fassan, M., Bicciato, S., Cordenonsi, M., & Piccolo, S. (2018). Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4. Nature Medicine, 24(10), 1599–1610. https://doi.org/10.1038/s41591-018-0158-8CrossRefPubMedPubMedCentral

59.

Yamazaki, M., Hino, S., Usuki, S., Miyazaki, Y., Oda, T., Nakao, M., Ito, T., & Yamagata, K. (2023). YAP/BRD4-controlled ROR1 promotes tumor-initiating cells and hyperproliferation in pancreatic cancer. EMBO Journal, e112614. https://doi.org/10.15252/embj.2022112614

60.

Tu, M., Klein, L., Espinet, E., Georgomanolis, T., Wegwitz, F., Li, X., Urbach, L., Danieli-Mackay, A., Kuffer, S., Bojarczuk, K., Mizi, A., Gunesdogan, U., Chapuy, B., Gu, Z., Neesse, A., Kishore, U., Strobel, P., Hessmann, E., Hahn, S. A., & Singh, S. K. (2021). TNF-alpha-producing macrophages determine subtype identity and prognosis via AP1 enhancer reprogramming in pancreatic cancer. Nature Cancer, 2(11), 1185–1203. https://doi.org/10.1038/s43018-021-00258-wCrossRefPubMed

61.

Murakami, S., White, S. M., McIntosh, A. T., Nguyen, C. D. K., & Yi, C. (2023). Spontaneously evolved progenitor niches escape Yap oncogene addiction in advanced pancreatic ductal adenocarcinomas. Nature Commununications, 14(1), 1443. https://doi.org/10.1038/s41467-023-37147-yCrossRef

62.

Scarpa, A., Chang, D. K., Nones, K., Corbo, V., Patch, A. M., Bailey, P., Lawlor, R. T., Johns, A. L., Miller, D. K., Mafficini, A., Rusev, B., Scardoni, M., Antonello, D., Barbi, S., Sikora, K. O., Cingarlini, S., Vicentini, C., McKay, S., Quinn, M. C., & Grimmond, S. M. (2017). Whole-genome landscape of pancreatic neuroendocrine tumours. Nature, 543(7643), 65–71. https://doi.org/10.1038/nature21063CrossRefPubMed

63.

Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., Velculescu, V. E., Diaz, L. A., Jr., Vogelstein, B., Kinzler, K. W., Hruban, R. H., & Papadopoulos, N. (2011). DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science, 331(6021), 1199–1203. https://doi.org/10.1126/science.1200609CrossRefPubMedPubMedCentral

64.

Hackeng, W. M., Brosens, L. A., Poruk, K. E., Noe, M., Hosoda, W., Poling, J. S., Rizzo, A., Campbell-Thompson, M., Atkinson, M. A., Konukiewitz, B., Kloppel, G., Heaphy, C. M., Meeker, A. K., & Wood, L. D. (2016). Aberrant menin expression is an early event in pancreatic neuroendocrine tumorigenesis. Human Pathology, 56, 93–100. https://doi.org/10.1016/j.humpath.2016.06.006CrossRefPubMed

65.

Samdani, R. T., Wasylishen, A. R., Halperin, D. M., Dasari, A., Yao, J. C., Rashid, A., & Estrella, J. S. (2019). Loss of menin expression by immunohistochemistry in pancreatic neuroendocrine tumors: Comparison between primary and metastatic tumors. Pancreas, 48(4), 510–513. https://doi.org/10.1097/MPA.0000000000001274CrossRefPubMed

66.

Xu, J., Ye, Z., Zhuo, Q., Gao, H., Qin, Y., Lou, X., Zhang, W., Wang, F., Wang, Y., Jing, D., Fan, G., Zhang, Y., Chen, X., Chen, J., Xu, X., Yu, X., & Ji, S. (2023). MEN1 degradation induced by neddylation and the CUL4B-DCAF7 axis promotes pancreatic neuroendocrine tumor progression. Cancer Research, 83(13), 2226–2247. https://doi.org/10.1158/0008-5472.CAN-22-3599CrossRefPubMed

67.

Yi, Z., Wei, S., Jin, L., Jeyarajan, S., Yang, J., Gu, Y., Kim, H. S., Schechter, S., Lu, S., Paulsen, M. T., Bedi, K., Narayanan, I. V., Ljungman, M., Crawford, H. C., Pasca di Magliano, M., Ge, K., Dou, Y., & Shi, J. (2022). KDM6A regulates cell plasticity and pancreatic cancer progression by noncanonical activin pathway. Cellular and Molecular Gastroenterology and Hepatology, 13(2), 643–667. https://doi.org/10.1016/j.jcmgh.2021.09.014CrossRefPubMed

68.

Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A. M., Gingras, M. C., Miller, D. K., Christ, A. N., Bruxner, T. J., Quinn, M. C., Nourse, C., Murtaugh, L. C., Harliwong, I., Idrisoglu, S., Manning, S., Nourbakhsh, E., Wani, S., Fink, L., Holmes, O., & Grimmond, S. M. (2016). Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531(7592), 47–52. https://doi.org/10.1038/nature16965CrossRefPubMed

69.

Krauss, L., Urban, B. C., Hastreiter, S., Schneider, C., Wenzel, P., Hassan, Z., Wirth, M., Lankes, K., Terrasi, A., Klement, C., Cernilogar, F. M., Ollinger, R., de Andrade Kratzig, N., Engleitner, T., Schmid, R. M., Steiger, K., Rad, R., Kramer, O. H., Reichert, M., & Schneider, G. (2021). HDAC2 facilitates pancreatic cancer metastasis. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-3209

70.

Patil, S., Steuber, B., Kopp, W., Kari, V., Urbach, L., Wang, X., Kuffer, S., Bohnenberger, H., Spyropoulou, D., Zhang, Z., Versemann, L., Bosherz, M. S., Brunner, M., Gaedcke, J., Strobel, P., Zhang, J. S., Neesse, A., Ellenrieder, V., Singh, S. K., & Hessmann, E. (2020). EZH2 regulates pancreatic cancer subtype identity and tumor progression via transcriptional repression of GATA6. Cancer Research, 80(21), 4620–4632. https://doi.org/10.1158/0008-5472.CAN-20-0672CrossRefPubMed

71.

Dandawate, P., Ghosh, C., Palaniyandi, K., Paul, S., Rawal, S., Pradhan, R., Sayed, A. A. A., Choudhury, S., Standing, D., Subramaniam, D., Padhye, S. B., Gunewardena, S., Thomas, S. M., Neil, M. O., Tawfik, O., Welch, D. R., Jensen, R. A., Maliski, S., Weir, S., & Dhar, A. (2019). The histone demethylase KDM3A, increased in human pancreatic tumors, regulates expression of DCLK1 and promotes tumorigenesis in mice. Gastroenterology, 157(6), 1646–1659 e1611. https://doi.org/10.1053/j.gastro.2019.08.018CrossRefPubMed

72.

Kalisz, M., Bernardo, E., Beucher, A., Maestro, M. A., Del Pozo, N., Millan, I., Haeberle, L., Schlensog, M., Safi, S. A., Knoefel, W. T., Grau, V., de Vas, M., Shpargel, K. B., Vaquero, E., Magnuson, T., Ortega, S., Esposito, I., Real, F. X., & Ferrer, J. (2020). HNF1A recruits KDM6A to activate differentiated acinar cell programs that suppress pancreatic cancer. The EMBO Journal, 39(9), e102808. https://doi.org/10.15252/embj.2019102808CrossRefPubMedPubMedCentral

73.

Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., Cerami, E., Sander, C., & Schultz, N. (2013). Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Science Signaling, 6(269), pl1. https://doi.org/10.1126/scisignal.2004088CrossRefPubMedPubMedCentral

74.

Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., Antipin, Y., Reva, B., Goldberg, A. P., Sander, C., & Schultz, N. (2012). The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discovery, 2(5), 401–404. https://doi.org/10.1158/2159-8290.CD-12-0095CrossRefPubMed

75.

Barski, A., Cuddapah, S., Cui, K., Roh, T. Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007). High-resolution profiling of histone methylations in the human genome. Cell, 129(4), 823–837. https://doi.org/10.1016/j.cell.2007.05.009CrossRefPubMed

76.

Bernstein, B. E., Humphrey, E. L., Erlich, R. L., Schneider, R., Bouman, P., Liu, J. S., Kouzarides, T., & Schreiber, S. L. (2002). Methylation of histone H3 Lys 4 in coding regions of active genes. Proceedings of the National Academy of Sciences, 99(13), 8695–8700. https://doi.org/10.1073/pnas.082249499CrossRef

77.

Bernstein, B. E., Kamal, M., Lindblad-Toh, K., Bekiranov, S., Bailey, D. K., Huebert, D. J., McMahon, S., Karlsson, E. K., Kulbokas, E. J., 3rd, Gingeras, T. R., Schreiber, S. L., & Lander, E. S. (2005). Genomic maps and comparative analysis of histone modifications in human and mouse. Cell, 120(2), 169–181. https://doi.org/10.1016/j.cell.2005.01.001CrossRefPubMed

78.

Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., Wang, W., Weng, Z., Green, R. D., Crawford, G. E., & Ren, B. (2007). Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nature Genetics, 39(3), 311–318. https://doi.org/10.1038/ng1966CrossRefPubMed

79.

Sausen, M., Phallen, J., Adleff, V., Jones, S., Leary, R. J., Barrett, M. T., Anagnostou, V., Parpart-Li, S., Murphy, D., Kay Li, Q., Hruban, C. A., Scharpf, R., White, J. R., O’Dwyer, P. J., Allen, P. J., Eshleman, J. R., Thompson, C. B., Klimstra, D. S., Linehan, D. C., & Velculescu, V. E. (2015). Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nature Communications, 6, 7686. https://doi.org/10.1038/ncomms8686CrossRefPubMed

80.

Mozzetta, C., Boyarchuk, E., Pontis, J., & Ait-Si-Ali, S. (2015). Sound of silence: The properties and functions of repressive Lys methyltransferases. Nature Reviews Molecular Cell Biology, 16(8), 499–513. https://doi.org/10.1038/nrm4029CrossRefPubMed

81.

Schulz, W. A., Lang, A., Koch, J., & Greife, A. (2019). The histone demethylase UTX/KDM6A in cancer: Progress and puzzles. International Journal of Cancer, 145(3), 614–620. https://doi.org/10.1002/ijc.32116CrossRefPubMed

82.

Yang, J., Jin, L., Kim, H. S., Tian, F., Yi, Z., Bedi, K., Ljungman, M., Pasca di Magliano, M., Crawford, H., & Shi, J. (2022). KDM6A loss recruits tumor-associated neutrophils and promotes neutrophil extracellular trap formation in pancreatic cancer. Cancer Research, 82(22), 4247–4260. https://doi.org/10.1158/0008-5472.CAN-22-0968CrossRefPubMedPubMedCentral

83.

Revia, S., Seretny, A., Wendler, L., Banito, A., Eckert, C., Breuer, K., Mayakonda, A., Lutsik, P., Evert, M., Ribback, S., Gallage, S., Chikh Bakri, I., Breuhahn, K., Schirmacher, P., Heinrich, S., Gaida, M. M., Heikenwalder, M., Calvisi, D. F., Plass, C., & Tschaharganeh, D. F. (2022). Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer. Gut, 71(8), 1613–1628. https://doi.org/10.1136/gutjnl-2021-325405CrossRefPubMed

84.

Watanabe, S., Shimada, S., Akiyama, Y., Ishikawa, Y., Ogura, T., Ogawa, K., Ono, H., Mitsunori, Y., Ban, D., Kudo, A., Yamaoka, S., Tanabe, M., & Tanaka, S. (2019). Loss of KDM6A characterizes a poor prognostic subtype of human pancreatic cancer and potentiates HDAC inhibitor lethality. International Journal of Cancer, 145(1), 192–205. https://doi.org/10.1002/ijc.32072CrossRefPubMed

85.

Piunti, A., & Shilatifard, A. (2021). The roles of polycomb repressive complexes in mammalian development and cancer. Nature Reviews. Molecular Cell Biology, 22(5), 326–345. https://doi.org/10.1038/s41580-021-00341-1CrossRefPubMed

86.

Mallen-St Clair, J., Soydaner-Azeloglu, R., Lee, K. E., Taylor, L., Livanos, A., Pylayeva-Gupta, Y., Miller, G., Margueron, R., Reinberg, D., & Bar-Sagi, D. (2012). EZH2 couples pancreatic regeneration to neoplastic progression. Genes & Development, 26(5), 439–444. https://doi.org/10.1101/gad.181800.111CrossRef

87.

Martinelli, P., Pau, C.-d. S., & E., Cox, T., Sainz, B., Jr., Dusetti, N., Greenhalf, W., Rinaldi, L., Costello, E., Ghaneh, P., Malats, N., Buchler, M., Pajic, M., Biankin, A. V., Iovanna, J., Neoptolemos, J., & Real, F. X. (2017). GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut, 66(9), 1665–1676. https://doi.org/10.1136/gutjnl-2015-311256CrossRefPubMed

88.

Versemann, L., Patil, S., Steuber, B., Zhang, Z., Kopp, W., Krawczyk, H. E., Kaulfuss, S., Wollnik, B., Strobel, P., Neesse, A., Singh, S. K., Ellenrieder, V., & Hessmann, E. (2022). TP53-status-dependent oncogenic EZH2 activity in pancreatic cancer. Cancers (Basel), 14(14). https://doi.org/10.3390/cancers14143451

89.

Chibaya, L., Murphy, K. C., DeMarco, K. D., Gopalan, S., Liu, H., Parikh, C. N., Lopez-Diaz, Y., Faulkner, M., Li, J., Morris, J. P., Ho, Y. J., Chana, S. K., Simon, J., Luan, W., Kulick, A., de Stanchina, E., Simin, K., Zhu, L. J., Fazzio, T. G., & Ruscetti, M. (2023). EZH2 inhibition remodels the inflammatory senescence-associated secretory phenotype to potentiate pancreatic cancer immune surveillance. Nature Cancer. https://doi.org/10.1038/s43018-023-00553-8

90.

Dawkins, J. B., Wang, J., Maniati, E., Heward, J. A., Koniali, L., Kocher, H. M., Martin, S. A., Chelala, C., Balkwill, F. R., Fitzgibbon, J., & Grose, R. P. (2016). Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma. Cancer Research, 76(16), 4861–4871. https://doi.org/10.1158/0008-5472.CAN-16-0481CrossRefPubMedPubMedCentral

91.

Koutsioumpa, M., Hatziapostolou, M., Polytarchou, C., Tolosa, E. J., Almada, L. L., Mahurkar-Joshi, S., Williams, J., Tirado-Rodriguez, A. B., Huerta-Yepez, S., Karavias, D., Kourea, H., Poultsides, G. A., Struhl, K., Dawson, D. W., Donahue, T. R., Fernandez-Zapico, M. E., & Iliopoulos, D. (2019). Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut, 68(7), 1271–1286. https://doi.org/10.1136/gutjnl-2017-315690CrossRefPubMed

92.

Lu, S., Kim, H. S., Cao, Y., Bedi, K., Zhao, L., Narayanan, I. V., Magnuson, B., Gu, Y., Yang, J., Yi, Z., Babaniamansour, S., Shameon, S., Xu, C., Paulsen, M. T., Qiu, P., Jeyarajan, S., Ljungman, M., Thomas, D., Dou, Y., & Shi, J. (2023). KMT2D links TGF-beta signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity. International Journal of Cancer. https://doi.org/10.1002/ijc.34528

93.

Li, W., Wu, L., Jia, H., Lin, Z., Zhong, R., Li, Y., Jiang, C., Liu, S., Zhou, X., & Zhang, E. (2021). The low-complexity domains of the KMT2D protein regulate histone monomethylation transcription to facilitate pancreatic cancer progression. Cellular & Molecular Biology Letters, 26(1), 45. https://doi.org/10.1186/s11658-021-00292-7CrossRef

94.

Yang, G., Yuan, Y., Yuan, H., Wang, J., Yun, H., Geng, Y., Zhao, M., Li, L., Weng, Y., Liu, Z., Feng, J., Bu, Y., Liu, L., Wang, B., & Zhang, X. (2021). Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis. EMBO Reports, 22(2), e50967. https://doi.org/10.15252/embr.202050967CrossRefPubMed

95.

Wang, Y., Guo, Y. R., Liu, K., Yin, Z., Liu, R., Xia, Y., Tan, L., Yang, P., Lee, J. H., Li, X. J., Hawke, D., Zheng, Y., Qian, X., Lyu, J., He, J., Xing, D., Tao, Y. J., & Lu, Z. (2017). KAT2A coupled with the alpha-KGDH complex acts as a histone H3 succinyltransferase. Nature, 552(7684), 273–277. https://doi.org/10.1038/nature25003CrossRefPubMedPubMedCentral

96.

Liu, J., Shangguan, Y., Tang, D., & Dai, Y. (2021). Histone succinylation and its function on the nucleosome. Journal of Cellular and Molecular Medicine, 25(15), 7101–7109. https://doi.org/10.1111/jcmm.16676CrossRefPubMedPubMedCentral

97.

Tong, Y., Guo, D., Yan, D., Ma, C., Shao, F., Wang, Y., Luo, S., Lin, L., Tao, J., Jiang, Y., Lu, Z., & Xing, D. (2020). KAT2A succinyltransferase activity-mediated 14-3-3zeta upregulation promotes beta-catenin stabilization-dependent glycolysis and proliferation of pancreatic carcinoma cells. Cancer Letters, 469, 1–10. https://doi.org/10.1016/j.canlet.2019.09.015CrossRefPubMed

98.

Roth, S. Y., Denu, J. M., & Allis, C. D. (2001). Histone acetyltransferases. Annual Review of Biochemistry, 70, 81–120. https://doi.org/10.1146/annurev.biochem.70.1.81CrossRefPubMed

99.

Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., & Nakatani, Y. (1996). The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell, 87(5), 953–959. https://doi.org/10.1016/s0092-8674(00)82001-2CrossRefPubMed

100.

Garcia-Carpizo, V., Ruiz-Llorente, S., Sarmentero, J., Grana-Castro, O., Pisano, D. G., & Barrero, M. J. (2018). CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation. Epigenetics & Chromatin, 11(1), 30. https://doi.org/10.1186/s13072-018-0197-xCrossRef

101.

Furlan, T., Kirchmair, A., Sampson, N., Puhr, M., Gruber, M., Trajanoski, Z., Santer, F. R., Parson, W., Handle, F., & Culig, Z. (2021). MYC-mediated ribosomal gene expression sensitizes enzalutamide-resistant prostate cancer cells to EP300/CREBBP inhibitors. The American Journal of Pathology, 191(6), 1094–1107. https://doi.org/10.1016/j.ajpath.2021.02.017CrossRefPubMed

102.

Zhong, Z., Harmston, N., Wood, K. C., Madan, B., & Virshup, D. M. (2022). A p300/GATA6 axis determines differentiation and Wnt dependency in pancreatic cancer models. The Journal of Clinical Investigation, 132(12). https://doi.org/10.1172/JCI156305

103.

Proffitt, K. D., & Virshup, D. M. (2012). Precise regulation of porcupine activity is required for physiological Wnt signaling. The Journal of Biological Chemistry, 287(41), 34167–34178. https://doi.org/10.1074/jbc.M112.381970CrossRefPubMedPubMedCentral

104.

Miranda, M., Galli, L. M., Enriquez, M., Szabo, L. A., Gao, X., Hannoush, R. N., & Burrus, L. W. (2014). Identification of the WNT1 residues required for palmitoylation by porcupine. FEBS Letters, 588(24), 4815–4824. https://doi.org/10.1016/j.febslet.2014.11.016CrossRefPubMedPubMedCentral

105.

Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., & Gabriel, S. B. (2017). Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell, 32(2), 185–203 e113. https://doi.org/10.1016/j.ccell.2017.07.007CrossRef

106.

Hao, H. X., Xie, Y., Zhang, Y., Charlat, O., Oster, E., Avello, M., Lei, H., Mickanin, C., Liu, D., Ruffner, H., Mao, X., Ma, Q., Zamponi, R., Bouwmeester, T., Finan, P. M., Kirschner, M. W., Porter, J. A., Serluca, F. C., & Cong, F. (2012). ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature, 485(7397), 195–200. https://doi.org/10.1038/nature11019CrossRefPubMed

107.

Koo, B. K., Spit, M., Jordens, I., Low, T. Y., Stange, D. E., van de Wetering, M., van Es, J. H., Mohammed, S., Heck, A. J., Maurice, M. M., & Clevers, H. (2012). Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature, 488(7413), 665–669. https://doi.org/10.1038/nature11308CrossRefPubMed

108.

Jiang, X., Hao, H. X., Growney, J. D., Woolfenden, S., Bottiglio, C., Ng, N., Lu, B., Hsieh, M. H., Bagdasarian, L., Meyer, R., Smith, T. R., Avello, M., Charlat, O., Xie, Y., Porter, J. A., Pan, S., Liu, J., McLaughlin, M. E., & Cong, F. (2013). Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 110(31), 12649–12654. https://doi.org/10.1073/pnas.1307218110CrossRefPubMedPubMedCentral

109.

Mees, S. T., Mardin, W. A., Wendel, C., Baeumer, N., Willscher, E., Senninger, N., Schleicher, C., Colombo-Benkmann, M., & Haier, J. (2010). EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. International Journal of Cancer, 126(1), 114–124. https://doi.org/10.1002/ijc.24695CrossRefPubMed

110.

Ono, H., Basson, M. D., & Ito, H. (2016). P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. Oncotarget, 7(32), 51301–51310. https://doi.org/10.18632/oncotarget.10117CrossRefPubMedPubMedCentral

111.

Ono, H., Kato, T., Murase, Y., Nakamura, Y., Ishikawa, Y., Watanabe, S., Akahoshi, K., Ogura, T., Ogawa, K., Ban, D., Kudo, A., Akiyama, Y., Tanaka, S., Ito, H., & Tanabe, M. (2021). C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumor effects in pancreatic cancer. Scientific Reports, 11(1), 10078. https://doi.org/10.1038/s41598-021-89530-8CrossRefPubMedPubMedCentral

112.

Arensman, M. D., Telesca, D., Lay, A. R., Kershaw, K. M., Wu, N., Donahue, T. R., & Dawson, D. W. (2014). The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth. Molecular Cancer Therapeutics, 13(10), 2303–2314. https://doi.org/10.1158/1535-7163.MCT-13-1005CrossRefPubMedPubMedCentral

113.

Shi, Y. H., Xu, Q. C., Zhu, Y. Q., Liu, Z. D., Zhao, G. Y., Liu, Q., Wang, X. Y., Wang, J. Q., Xu, X., Su, Q., Lai, J. M., Huang, C. S., & Yin, X. Y. (2023). Imatinib facilitates gemcitabine sensitivity by targeting epigenetically activated PDGFC signaling in pancreatic cancer. Molecular Therapy, 31(2), 503–516. https://doi.org/10.1016/j.ymthe.2022.11.004CrossRefPubMed

114.

Weissmueller, S., Manchado, E., Saborowski, M., Morris, J. P., Wagenblast, E., Davis, C. A., Moon, S. H., Pfister, N. T., Tschaharganeh, D. F., Kitzing, T., Aust, D., Markert, E. K., Wu, J., Grimmond, S. M., Pilarsky, C., Prives, C., Biankin, A. V., & Lowe, S. W. (2014). Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor beta signaling. Cell, 157(2), 382–394. https://doi.org/10.1016/j.cell.2014.01.066CrossRefPubMedPubMedCentral

115.

Kurahara, H., Maemura, K., Mataki, Y., Sakoda, M., Shinchi, H., & Natsugoe, S. (2016). Impact of p53 and PDGFR-beta expression on metastasis and prognosis of patients with pancreatic cancer. World Journal of Surgery, 40(8), 1977–1984. https://doi.org/10.1007/s00268-016-3477-2CrossRefPubMed

116.

Principe, D. R., Xiong, R., Li, Y., Pham, T. N. D., Kamath, S. D., Dubrovskyi, O., Ratia, K., Huang, F., Zhao, J., Shen, Z., Thummuri, D., Daohong, Z., Underwood, P. W., Trevino, J., Munshi, H. G., Thatcher, G. R. J., & Rana, A. (2022). XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America, 119(4). https://doi.org/10.1073/pnas.2116764119

117.

Fan, P., Zhao, J., Meng, Z., Wu, H., Wang, B., Wu, H., & Jin, X. (2019). Overexpressed histone acetyltransferase 1 regulates cancer immunity by increasing programmed death-ligand 1 expression in pancreatic cancer. Journal of Experimental & Clinical Cancer Research, 38(1), 47. https://doi.org/10.1186/s13046-019-1044-zCrossRef

118.

Chen, C. H., Chuang, S. M., Yang, M. F., Liao, J. W., Yu, S. L., & Chen, J. J. (2012). A novel function of YWHAZ/beta-catenin axis in promoting epithelial-mesenchymal transition and lung cancer metastasis. Molecular Cancer Research, 10(10), 1319–1331. https://doi.org/10.1158/1541-7786.MCR-12-0189CrossRefPubMed

119.

Seto, E., & Yoshida, M. (2014). Erasers of histone acetylation: The histone deacetylase enzymes. Cold Spring Harbor Perspectives in Biology, 6(4), a018713. https://doi.org/10.1101/cshperspect.a018713CrossRefPubMedPubMedCentral

120.

Haberland, M., Montgomery, R. L., & Olson, E. N. (2009). The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nature Reviews. Genetics, 10(1), 32–42. https://doi.org/10.1038/nrg2485CrossRefPubMedPubMedCentral

121.

Schwer, B., & Verdin, E. (2008). Conserved metabolic regulatory functions of sirtuins. Cell Metabolism, 7(2), 104–112. https://doi.org/10.1016/j.cmet.2007.11.006CrossRefPubMed

122.

Parbin, S., Kar, S., Shilpi, A., Sengupta, D., Deb, M., Rath, S. K., & Patra, S. K. (2014). Histone deacetylases: A saga of perturbed acetylation homeostasis in cancer. The Journal of Histochemistry and Cytochemistry, 62(1), 11–33. https://doi.org/10.1369/0022155413506582CrossRefPubMedPubMedCentral

123.

Bannister, A. J., & Kouzarides, T. (2011). Regulation of chromatin by histone modifications. Cell Research, 21(3), 381–395. https://doi.org/10.1038/cr.2011.22CrossRefPubMedPubMedCentral

124.

Kelly, R. D., & Cowley, S. M. (2013). The physiological roles of histone deacetylase (HDAC) 1 and 2: Complex co-stars with multiple leading parts. Biochemical Society Transactions, 41(3), 741–749. https://doi.org/10.1042/BST20130010CrossRefPubMed

125.

Shi, X., Hong, T., Walter, K. L., Ewalt, M., Michishita, E., Hung, T., Carney, D., Pena, P., Lan, F., Kaadige, M. R., Lacoste, N., Cayrou, C., Davrazou, F., Saha, A., Cairns, B. R., Ayer, D. E., Kutateladze, T. G., Shi, Y., Cote, J., & Gozani, O. (2006). ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature, 442(7098), 96–99. https://doi.org/10.1038/nature04835CrossRefPubMedPubMedCentral

126.

Lehmann, A., Denkert, C., Budczies, J., Buckendahl, A. C., Darb-Esfahani, S., Noske, A., Muller, B. M., Bahra, M., Neuhaus, P., Dietel, M., Kristiansen, G., & Weichert, W. (2009). High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo. BMC Cancer, 9, 395. https://doi.org/10.1186/1471-2407-9-395CrossRefPubMedPubMedCentral

127.

Fritsche, P., Seidler, B., Schuler, S., Schnieke, A., Gottlicher, M., Schmid, R. M., Saur, D., & Schneider, G. (2009). HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA. Gut, 58(10), 1399–1409. https://doi.org/10.1136/gut.2009.180711CrossRefPubMed

128.

Cai, M. H., Xu, X. G., Yan, S. L., Sun, Z., Ying, Y., Wang, B. K., & Tu, Y. X. (2018). Depletion of HDAC1, 7 and 8 by histone deacetylase inhibition confers elimination of pancreatic cancer stem cells in combination with gemcitabine. Scientific Reports, 8(1), 1621. https://doi.org/10.1038/s41598-018-20004-0CrossRefPubMedPubMedCentral

129.

Shinke, G., Yamada, D., Eguchi, H., Iwagami, Y., Asaoka, T., Noda, T., Wada, H., Kawamoto, K., Gotoh, K., Kobayashi, S., Takeda, Y., Tanemura, M., Mori, M., & Doki, Y. (2018). Role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer. Cancer Science, 109(8), 2520–2531. https://doi.org/10.1111/cas.13700CrossRefPubMedPubMedCentral

130.

Li, J., Wang, J., Wang, J., Nawaz, Z., Liu, J. M., Qin, J., & Wong, J. (2000). Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. The EMBO Journal, 19(16), 4342–4350. https://doi.org/10.1093/emboj/19.16.4342CrossRefPubMedPubMedCentral

131.

You, A., Tong, J. K., Grozinger, C. M., & Schreiber, S. L. (2001). CoREST is an integral component of the CoREST- human histone deacetylase complex. Proceedings of the National Academy of Sciences of the United States of America, 98(4), 1454–1458. https://doi.org/10.1073/pnas.98.4.1454CrossRefPubMedPubMedCentral

132.

von Burstin, J., Eser, S., Paul, M. C., Seidler, B., Brandl, M., Messer, M., von Werder, A., Schmidt, A., Mages, J., Pagel, P., Schnieke, A., Schmid, R. M., Schneider, G., & Saur, D. (2009). E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology, 137(1), 361–371. https://doi.org/10.1053/j.gastro.2009.04.004CrossRef

133.

Mishra, V. K., Wegwitz, F., Kosinsky, R. L., Sen, M., Baumgartner, R., Wulff, T., Siveke, J. T., Schildhaus, H. U., Najafova, Z., Kari, V., Kohlhof, H., Hessmann, E., & Johnsen, S. A. (2017). Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4- and MYC-dependent manner. Nucleic Acids Research, 45(11), 6334–6349. https://doi.org/10.1093/nar/gkx212CrossRefPubMedPubMedCentral

134.

Ramaker, R. C., Hardigan, A. A., Gordon, E. R., Wright, C. A., Myers, R. M., & Cooper, S. J. (2021). Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition. BMC Cancer, 21(1), 632. https://doi.org/10.1186/s12885-021-08388-1CrossRefPubMedPubMedCentral

135.

Diener, J., Baggiolini, A., Pernebrink, M., Dalcher, D., Lerra, L., Cheng, P. F., Varum, S., Hausel, J., Stierli, S., Treier, M., Studer, L., Basler, K., Levesque, M. P., Dummer, R., Santoro, R., Cantu, C., & Sommer, L. (2021). Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4. Nature Communications, 12(1), 5056. https://doi.org/10.1038/s41467-021-25326-8CrossRefPubMedPubMedCentral

136.

UniProt, C. (2021). UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Research, 49(D1), D480–D489. https://doi.org/10.1093/nar/gkaa1100CrossRef

137.

Goujon, M., McWilliam, H., Li, W., Valentin, F., Squizzato, S., Paern, J., & Lopez, R. (2010). A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Research, 38(Web Server issue), W695–W699. https://doi.org/10.1093/nar/gkq313CrossRefPubMedPubMedCentral

138.

Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J., & Higgins, D. G. (2007). Clustal W and Clustal X version 2.0. Bioinformatics, 23(21), 2947–2948. https://doi.org/10.1093/bioinformatics/btm404CrossRefPubMed

139.

Xu, S., Dai, Z., Guo, P., Fu, X., Liu, S., Zhou, L., Tang, W., Feng, T., Chen, M., Zhan, L., Wu, T., Hu, E., Jiang, Y., Bo, X., & Yu, G. (2021). ggtreeExtra: Compact visualization of richly annotated phylogenetic data. Molecular Biology and Evolution, 38(9), 4039–4042. https://doi.org/10.1093/molbev/msab166CrossRefPubMedPubMedCentral

140.

Ghandi, M., Huang, F. W., Jane-Valbuena, J., Kryukov, G. V., Lo, C. C., McDonald, E. R., 3rd, Barretina, J., Gelfand, E. T., Bielski, C. M., Li, H., Hu, K., Andreev-Drakhlin, A. Y., Kim, J., Hess, J. M., Haas, B. J., Aguet, F., Weir, B. A., Rothberg, M. V., Paolella, B. R., & Sellers, W. R. (2019). Next-generation characterization of the cancer cell line encyclopedia. Nature, 569(7757), 503–508. https://doi.org/10.1038/s41586-019-1186-3CrossRefPubMedPubMedCentral

141.

DepMap, B. (2022). DepMap 22Q4 Public (Version 2). figshare. https://figshare.com/articles/dataset/DepMap_22Q4_Public/21637199/2

142.

Jin, X., Demere, Z., Nair, K., Ali, A., Ferraro, G. B., Natoli, T., Deik, A., Petronio, L., Tang, A. A., Zhu, C., Wang, L., Rosenberg, D., Mangena, V., Roth, J., Chung, K., Jain, R. K., Clish, C. B., Vander Heiden, M. G., & Golub, T. R. (2020). A metastasis map of human cancer cell lines. Nature, 588(7837), 331–336. https://doi.org/10.1038/s41586-020-2969-2CrossRefPubMedPubMedCentral

143.

Lechner, S., Malgapo, M. I. P., Gratz, C., Steimbach, R. R., Baron, A., Ruther, P., Nadal, S., Stumpf, C., Loos, C., Ku, X., Prokofeva, P., Lautenbacher, L., Heimburg, T., Wurf, V., Meng, C., Wilhelm, M., Sippl, W., Kleigrewe, K., Pauling, J. K., & Medard, G. (2022). Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nature Chemical Biology, 18(8), 812–820. https://doi.org/10.1038/s41589-022-01015-5CrossRefPubMedPubMedCentral

144.

Xiong, Y., Donovan, K. A., Eleuteri, N. A., Kirmani, N., Yue, H., Razov, A., Krupnick, N. M., Nowak, R. P., & Fischer, E. S. (2021). Chemo-proteomics exploration of HDAC degradability by small molecule degraders. Cell. Chemistry & Biology, 28(10), 1514–1527 e1514. https://doi.org/10.1016/j.chembiol.2021.07.002CrossRef

145.

Bond, M. J., Chu, L., Nalawansha, D. A., Li, K., & Crews, C. M. (2020). Targeted degradation of oncogenic KRAS(G12C) by VHL-recruiting PROTACs. ACS Central Science, 6(8), 1367–1375. https://doi.org/10.1021/acscentsci.0c00411CrossRefPubMedPubMedCentral

146.

Kaminskas, E., Farrell, A. T., Wang, Y. C., Sridhara, R., & Pazdur, R. (2005). FDA drug approval summary: Azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist, 10(3), 176–182. https://doi.org/10.1634/theoncologist.10-3-176CrossRefPubMed

147.

Kantarjian, H., Issa, J. P., Rosenfeld, C. S., Bennett, J. M., Albitar, M., DiPersio, J., Klimek, V., Slack, J., de Castro, C., Ravandi, F., Helmer, R., 3rd, Shen, L., Nimer, S. D., Leavitt, R., Raza, A., & Saba, H. (2006). Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer, 106(8), 1794–1803. https://doi.org/10.1002/cncr.21792CrossRefPubMed

148.

Barbarotta, L., & Hurley, K. (2015). Romidepsin for the treatment of peripheral T-cell lymphoma. Journal of the Advanced Practitioner in Oncology, 6(1), 22–36 https://www.ncbi.nlm.nih.gov/pubmed/26413372PubMedPubMedCentral

149.

Mann, B. S., Johnson, J. R., Cohen, M. H., Justice, R., & Pazdur, R. (2007). FDA approval summary: Vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist, 12(10), 1247–1252. https://doi.org/10.1634/theoncologist.12-10-1247CrossRefPubMed

150.

Hoy, S. M. (2020). Tazemetostat: First approval. Drugs, 80(5), 513–521. https://doi.org/10.1007/s40265-020-01288-xCrossRefPubMed

151.

Fraunhoffer, N. A., Moreno Vega, A. I., Abuelafia, A. M., Morvan, M., Lebarbier, E., Mary-Huard, T., Zimmermann, M., Lomberk, G., Urrutia, R., Dusetti, N., Blum, Y., Nicolle, R., & Iovanna, J. (2023). Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells. EBioMedicine, 92, 104602. https://doi.org/10.1016/j.ebiom.2023.104602CrossRefPubMedPubMedCentral

152.

Wong, K. K. (2020). DNMT1 as a therapeutic target in pancreatic cancer: Mechanisms and clinical implications. Cellular Oncology (Dordrecht), 43(5), 779–792. https://doi.org/10.1007/s13402-020-00526-4CrossRefPubMed

153.

Heumann, T. R., Baretti, M., Sugar, E. A., Durham, J. N., Linden, S., Lopez-Vidal, T. Y., Leatherman, J., Cope, L., Sharma, A., Weekes, C. D., O'Dwyer, P. J., Reiss, K. A., Monga, D. K., Ahuja, N., & Azad, N. S. (2022). A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence. Clinical Epigenetics, 14(1), 166. https://doi.org/10.1186/s13148-022-01367-8CrossRefPubMedPubMedCentral

154.

Booth, L., Poklepovic, A., & Dent, P. (2020). Neratinib decreases pro-survival responses of [sorafenib + vorinostat] in pancreatic cancer. Biochemical Pharmacology, 178, 114067. https://doi.org/10.1016/j.bcp.2020.114067CrossRefPubMed

155.

Jo, J. H., Jung, D. E., Lee, H. S., Park, S. B., Chung, M. J., Park, J. Y., Bang, S., Park, S. W., Cho, S., & Song, S. Y. (2022). A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma. International Journal of Cancer, 151(9), 1565–1577. https://doi.org/10.1002/ijc.34144CrossRefPubMedPubMedCentral

156.

Fang, Y., McGrail, D. J., Sun, C., Labrie, M., Chen, X., Zhang, D., Ju, Z., Vellano, C. P., Lu, Y., Li, Y., Jeong, K. J., Ding, Z., Liang, J., Wang, S. W., Dai, H., Lee, S., Sahni, N., Mercado-Uribe, I., Kim, T. B., & Mills, G. B. (2019). Sequential therapy with PARP and WEE1 inhibitors minimizes toxicity while maintaining efficacy. Cancer Cell, 35(6), 851–867 e857. https://doi.org/10.1016/j.ccell.2019.05.001CrossRefPubMedPubMedCentral

157.

Fernandes Neto, J. M., Nadal, E., Bosdriesz, E., Ooft, S. N., Farre, L., McLean, C., Klarenbeek, S., Jurgens, A., Hagen, H., Wang, L., Felip, E., Martinez-Marti, A., Vidal, A., Voest, E., Wessels, L. F. A., van Tellingen, O., Villanueva, A., & Bernards, R. (2020). Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours. Nature Communications, 11(1), 3157. https://doi.org/10.1038/s41467-020-16952-9CrossRefPubMedPubMedCentral

158.

Ozkan-Dagliyan, I., Diehl, J. N., George, S. D., Schaefer, A., Papke, B., Klotz-Noack, K., Waters, A. M., Goodwin, C. M., Gautam, P., Pierobon, M., Peng, S., Gilbert, T. S. K., Lin, K. H., Dagliyan, O., Wennerberg, K., Petricoin, E. F., 3rd, Tran, N. L., Bhagwat, S. V., Tiu, R. V., & Der, C. J. (2020). Low-dose vertical inhibition of the RAF-MEK-ERK cascade causes apoptotic death of KRAS mutant cancers. Cell Reports, 31(11), 107764. https://doi.org/10.1016/j.celrep.2020.107764CrossRefPubMed

159.

Wang, H., Cao, Q., & Dudek, A. Z. (2012). Phase II study of panobinostat and bortezomib in patients with pancreatic cancer progressing on gemcitabine-based therapy. Anticancer Research, 32(3), 1027–1031 https://www.ncbi.nlm.nih.gov/pubmed/22399627PubMed

160.

Connolly, R. M., Laille, E., Vaishampayan, U., Chung, V., Kelly, K., Dowlati, A., Alese, O. B., Harvey, R. D., Haluska, P., Siu, L. L., Kummar, S., Piekarz, R., Ivy, S. P., Anders, N. M., Downs, M., O’Connor, A., Scardina, A., Saunders, J., Rosner, G. L., & Team, E.-S. (2020). Phase I and pharmacokinetic study of romidepsin in patients with cancer and hepatic dysfunction: A national cancer institute organ dysfunction working group study. Clinical Cancer Research, 26(20), 5329–5337. https://doi.org/10.1158/1078-0432.CCR-20-1412CrossRefPubMedPubMedCentral

161.

Chan, E., Arlinghaus, L. R., Cardin, D. B., Goff, L., Berlin, J. D., Parikh, A., Abramson, R. G., Yankeelov, T. E., Hiebert, S., Merchant, N., Bhaskara, S., & Chakravarthy, A. B. (2016). Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Radiotherapy and Oncology, 119(2), 312–318. https://doi.org/10.1016/j.radonc.2016.04.013CrossRefPubMedPubMedCentral

162.

Gounder, M., Schoffski, P., Jones, R. L., Agulnik, M., Cote, G. M., Villalobos, V. M., Attia, S., Chugh, R., Chen, T. W., Jahan, T., Loggers, E. T., Gupta, A., Italiano, A., Demetri, G. D., Ratan, R., Davis, L. E., Mir, O., Dileo, P., Van Tine, B. A., & Stacchiotti, S. (2020). Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: An international, open-label, phase 2 basket study. The Lancet Oncology, 21(11), 1423–1432. https://doi.org/10.1016/S1470-2045(20)30451-4CrossRefPubMed

163.

Sohal, D., Krishnamurthi, S., Tohme, R., Gu, X., Lindner, D., Landowski, T. H., Pink, J., Radivoyevitch, T., Fada, S., Lee, Z., Shepard, D., Khorana, A., & Saunthararajah, Y. (2020). A pilot clinical trial of the cytidine deaminase inhibitor tetrahydrouridine combined with decitabine to target DNMT1 in advanced, chemorefractory pancreatic cancer. American Journal of Cancer Research, 10(9), 3047–3060 https://www.ncbi.nlm.nih.gov/pubmed/33042633PubMedPubMedCentral

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At a glance: The STEP trials

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