Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 3/2017

01-09-2017

Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma

Authors: Keiichi Koshizuka, Toyoyuki Hanazawa, Takayuki Arai, Atsushi Okato, Naoko Kikkawa, Naohiko Seki

Published in: Cancer and Metastasis Reviews | Issue 3/2017

Login to get access

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that act as fine-tuners of the post-transcriptional control of protein-coding or noncoding RNAs by repressing translation or cleaving RNA transcripts in a sequence-dependent manner in cells. Accumulating evidence have been indicated that aberrantly expressed miRNAs are deeply involved in human pathogenesis, including cancers. Surprisingly, these small, single-stranded RNAs (18–23 nucleotides) have been shown to function as antitumor or oncogenic RNAs in several types of cancer cells. A single miRNA has regulating hundreds or thousands of different mRNAs, and individual mRNA has been regulated by multiple different miRNAs in normal cells. Therefore, tightly controlled RNA networks can be disrupted by dysregulated of miRNAs in cancer cells. Investigation of novel miRNA-mediated RNA networks in cancer cells could provide new insights in the field of cancer research. In this review, we focus on head and neck squamous cell carcinoma (HNSCC) and discuss current findings of the involvement of aberrantly expressed miRNAs in the pathogenesis of HNSCC.
Literature
1.
Bhartiya, D., & Scaria, V. (2016). Genomic variations in non-coding RNAs: structure, function and regulation. Genomics, 107(2–3), 59–68.PubMedCrossRef
2.
Beermann, J., Piccoli, M. T., Viereck, J., & Thum, T. (2016). Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev, 96(4), 1297–1325.PubMedCrossRef
3.
Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297.PubMedCrossRef
4.
5.
Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 19(1), 92–105.PubMedPubMedCentralCrossRef
6.
7.
Nelson, K. M., & Weiss, G. J. (2008). MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther, 7(12), 3655–3660.PubMedCrossRef
8.
9.
Wang, Y., Hou, J., He, D., Sun, M., Zhang, P., Yu, Y., et al. (2016). The emerging function and mechanism of ceRNAs in cancer. Trends Genet, 32(4), 211–224.PubMedPubMedCentralCrossRef
10.
Chen, L., Zhang, S., Wu, J., Cui, J., Zhong, L., Zeng, L., et al. (2017). circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family. Oncogene. doi:10.​1038/​onc.​2017.​89.
11.
Leemans, C. R., Braakhuis, B. J., & Brakenhoff, R. H. (2011). The molecular biology of head and neck cancer. Nat Rev Cancer, 11(1), 9–22.PubMedCrossRef
12.
Siegel, R. L., Miller, K. D., & Jemal, A. (2016). Cancer statistics, 2016. CA Cancer J Clin, 66(1), 7–30.PubMedCrossRef
13.
Janiszewska, J., Szaumkessel, M., & Szyfter, K. (2013). microRNAs are important players in head and neck carcinoma: a review. Crit Rev Oncol Hematol, 88(3), 716–728.PubMedCrossRef
14.
Chung, C. H., Guthrie, V. B., Masica, D. L., Tokheim, C., Kang, H., Richmon, J., et al. (2015). Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol, 26(6), 1216–1223.PubMedPubMedCentralCrossRef
15.
16.
Lui, V. W., Hedberg, M. L., Li, H., Vangara, B. S., Pendleton, K., Zeng, Y., et al. (2013). Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov, 3(7), 761–769.PubMedPubMedCentralCrossRef
17.
Kulasinghe, A., Perry, C., Jovanovic, L., Nelson, C., & Punyadeera, C. (2015). Circulating tumour cells in metastatic head and neck cancers. Int J Cancer, 136(11), 2515–2523.PubMedCrossRef
18.
Ang, K. K., Zhang, Q., Rosenthal, D. I., Nguyen-Tan, P. F., Sherman, E. J., Weber, R. S., et al. (2014). Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol, 32(27), 2940–2950.PubMedPubMedCentralCrossRef
19.
Sethi, N., Wright, A., Wood, H., & Rabbitts, P. (2014). MicroRNAs and head and neck cancer: reviewing the first decade of research. Eur J Cancer, 50(15), 2619–2635.PubMedCrossRef
20.
Wiemer, E. A. (2007). The role of microRNAs in cancer: no small matter. Eur J Cancer, 43(10), 1529–1544.PubMedCrossRef
21.
Chen, D., Cabay, R. J., Jin, Y., Wang, A., Lu, Y., Shah-Khan, M., et al. (2013). MicroRNA deregulations in head and neck squamous cell carcinomas. J Oral Maxillofac Res, 4(1), e2.PubMedPubMedCentralCrossRef
22.
Zou, A. E., Zheng, H., Saad, M. A., Rahimy, M., Ku, J., Kuo, S. Z., et al. (2016). The non-coding landscape of head and neck squamous cell carcinoma. Oncotarget, 7(32), 51211–51222.PubMedPubMedCentralCrossRef
23.
Kikkawa, N., Hanazawa, T., Fujimura, L., Nohata, N., Suzuki, H., Chazono, H., et al. (2010). miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC). Br J Cancer, 103(6), 877–884.PubMedPubMedCentralCrossRef
24.
Nohata, N., Hanazawa, T., Kikkawa, N., Sakurai, D., Fujimura, L., Chiyomaru, T., et al. (2011). Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. Br J Cancer, 105(6), 833–841.PubMedPubMedCentralCrossRef
25.
Fukumoto, I., Kinoshita, T., Hanazawa, T., Kikkawa, N., Chiyomaru, T., Enokida, H., et al. (2014). Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature. Br J Cancer, 111(2), 386–394.PubMedPubMedCentralCrossRef
26.
Fukumoto, I., Hanazawa, T., Kinoshita, T., Kikkawa, N., Koshizuka, K., Goto, Y., et al. (2015). MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways. Br J Cancer, 112(5), 891–900.PubMedPubMedCentralCrossRef
27.
Koshizuka, K., Hanazawa, T., Fukumoto, I., Kikkawa, N., Matsushita, R., Mataki, H., et al. (2017). Dual-receptor (EGFR and c-MET) inhibition by tumor-suppressive miR-1 and miR-206 in head and neck squamous cell carcinoma. J Hum Genet, 62(1), 113–121.PubMedCrossRef
28.
Iorio, M. V., & Croce, C. M. (2012). MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med, 4(3), 143–159.PubMedPubMedCentralCrossRef
29.
30.
31.
Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., et al. (2005). TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature, 436(7051), 740–744.PubMedPubMedCentralCrossRef
32.
Gregory, R. I., Chendrimada, T. P., Cooch, N., & Shiekhattar, R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell, 123(4), 631–640.PubMedCrossRef
33.
Hutvagner, G., & Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297(5589), 2056–2060.PubMedCrossRef
34.
Matranga, C., Tomari, Y., Shin, C., Bartel, D. P., & Zamore, P. D. (2005). Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell, 123(4), 607–620.PubMedCrossRef
35.
Matsushita, R., Yoshino, H., Enokida, H., Goto, Y., Miyamoto, K., Yonemori, M., et al. (2016). Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): inhibition of bladder cancer cell aggressiveness. Oncotarget, 7(19), 28460–28487.PubMedPubMedCentralCrossRef
36.
Mataki, H., Seki, N., Mizuno, K., Nohata, N., Kamikawaji, K., Kumamoto, T., et al. (2016). Dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p) coordinately targeted MTDH in lung squamous cell carcinoma. Oncotarget, 7(44), 72084–72098.PubMedPubMedCentral
37.
Koshizuka, K., Nohata, N., Hanazawa, T., Kikkawa, N., Arai, T., Okato, A., et al. (2017). Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs. Oncotarget, 8(18), 30288–30304.PubMedPubMedCentral
38.
Koshizuka, K., Hanazawa, T., Kikkawa, N., Arai, T., Okato, A., Kurozumi, A., et al. (2017). Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer. Cancer Sci, 108(8), 1681-1692.
39.
Yang, J. S., & Lai, E. C. (2011). Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell, 43(6), 892–903.PubMedPubMedCentralCrossRef
40.
Sibley, C. R., Seow, Y., Saayman, S., Dijkstra, K. K., El Andaloussi, S., Weinberg, M. S., et al. (2012). The biogenesis and characterization of mammalian microRNAs of mirtron origin. Nucleic Acids Res, 40(1), 438–448.PubMedCrossRef
41.
Martin, R., Smibert, P., Yalcin, A., Tyler, D. M., Schafer, U., Tuschl, T., et al. (2009). A Drosophila pasha mutant distinguishes the canonical microRNA and mirtron pathways. Mol Cell Biol, 29(3), 861–870.PubMedCrossRef
42.
Hui, A. B., Lenarduzzi, M., Krushel, T., Waldron, L., Pintilie, M., Shi, W., et al. (2010). Comprehensive microRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res, 16(4), 1129–1139.PubMedCrossRef
43.
Liu, C. J., Tsai, M. M., Hung, P. S., Kao, S. Y., Liu, T. Y., Wu, K. J., et al. (2010). miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma. Cancer Res, 70(4), 1635–1644.PubMedCrossRef
44.
Lajer, C. B., Nielsen, F. C., Friis-Hansen, L., Norrild, B., Borup, R., Garnaes, E., et al. (2011). Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer, 104(5), 830–840.PubMedPubMedCentralCrossRef
45.
Severino, P., Bruggemann, H., Andreghetto, F. M., Camps, C., Klingbeil Mde, F., de Pereira, W. O., et al. (2013). MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation. BMC Cancer, 13, 533.PubMedPubMedCentralCrossRef
46.
Zhang, Y., Chen, Y., Yu, J., Liu, G., & Huang, Z. (2014). Integrated transcriptome analysis reveals miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma. Genomics, 104(4), 249–256.PubMedCrossRef
47.
Victoria Martinez, B., Dhahbi, J. M., Nunez Lopez, Y. O., Lamperska, K., Golusinski, P., Luczewski, L., et al. (2015). Circulating small non-coding RNA signature in head and neck squamous cell carcinoma. Oncotarget, 6(22), 19246–19263.PubMedCrossRef
48.
Wang, F., Lu, J., Peng, X., Wang, J., Liu, X., Chen, X., et al. (2016). Integrated analysis of microRNA regulatory network in nasopharyngeal carcinoma with deep sequencing. J Exp Clin Cancer Res, 35(1), 17.PubMedPubMedCentralCrossRef
49.
Xu, Y. F., Li, Y. Q., Guo, R., He, Q. M., Ren, X. Y., Tang, X. R., et al. (2015). Identification of miR-143 as a tumour suppressor in nasopharyngeal carcinoma based on microRNA expression profiling. Int J Biochem Cell Biol, 61, 120–128.PubMedCrossRef
50.
Manikandan, M., Deva Magendhra Rao, A. K., Arunkumar, G., Manickavasagam, M., Rajkumar, K. S., Rajaraman, R., et al. (2016). Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism. Mol Cancer, 15, 28.PubMedPubMedCentralCrossRef
51.
Lovat, F., Fassan, M., Gasparini, P., Rizzotto, L., Cascione, L., Pizzi, M., et al. (2015). miR-15b/16-2 deletion promotes B-cell malignancies. Proc Natl Acad Sci U S A, 112(37), 11636–11641.PubMedPubMedCentralCrossRef
52.
Singchat, W., Hitakomate, E., Rerkarmnuaychoke, B., Suntronpong, A., Fu, B., Bodhisuwan, W., et al. (2016). Genomic alteration in head and neck squamous cell carcinoma (HNSCC) cell lines inferred from karyotyping, molecular cytogenetics, and array comparative genomic hybridization. PLoS One, 11(8), e0160901.PubMedPubMedCentralCrossRef
53.
54.
Mataki, H., Enokida, H., Chiyomaru, T., Mizuno, K., Matsushita, R., Goto, Y., et al. (2015). Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C. J Hum Genet, 60(2), 53–61.PubMedCrossRef
55.
Nohata, N., Hanazawa, T., Kikkawa, N., Sakurai, D., Sasaki, K., Chiyomaru, T., et al. (2011). Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma. Int J Oncol, 39(5), 1099–1107.PubMed
56.
Baskerville, S., & Bartel, D. P. (2005). Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11(3), 241–247.PubMedPubMedCentralCrossRef
57.
Nohata, N., Hanazawa, T., Enokida, H., & Seki, N. (2012). microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget, 3(1), 9–21.PubMedPubMedCentralCrossRef
58.
Nohata, N., Sone, Y., Hanazawa, T., Fuse, M., Kikkawa, N., Yoshino, H., et al. (2011). miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma. Oncotarget, 2(1–2), 29–42.PubMedPubMedCentralCrossRef
59.
Du, Y. Y., Zhao, L. M., Chen, L., Sang, M. X., Li, J., Ma, M., et al. (2016). The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma. J Gastroenterol Hepatol, 31(2), 384–393.PubMedCrossRef
60.
Yoshino, H., Chiyomaru, T., Enokida, H., Kawakami, K., Tatarano, S., Nishiyama, K., et al. (2011). The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer. Br J Cancer, 104(5), 808–818.PubMedPubMedCentralCrossRef
61.
Yamasaki, T., Yoshino, H., Enokida, H., Hidaka, H., Chiyomaru, T., Nohata, N., et al. (2012). Novel molecular targets regulated by tumor suppressors microRNA-1 and microRNA-133a in bladder cancer. Int J Oncol, 40(6), 1821–1830.PubMed
62.
Kinoshita, T., Nohata, N., Watanabe-Takano, H., Yoshino, H., Hidaka, H., Fujimura, L., et al. (2012). Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma. Int J Oncol, 40(6), 1770–1778.PubMed
63.
Kinoshita, T., Nohata, N., Fuse, M., Hanazawa, T., Kikkawa, N., Fujimura, L., et al. (2012). Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun, 418(2), 378–383.PubMedCrossRef
64.
Yamamoto, N., Nishikawa, R., Chiyomaru, T., Goto, Y., Fukumoto, I., Usui, H., et al. (2015). The tumor-suppressive microRNA-1/133a cluster targets PDE7A and inhibits cancer cell migration and invasion in endometrial cancer. Int J Oncol, 47(1), 325–334.PubMedCrossRef
65.
Kent, O. A., McCall, M. N., Cornish, T. C., & Halushka, M. K. (2014). Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res, 42(12), 7528–7538.PubMedPubMedCentralCrossRef
66.
Yoshino, H., Enokida, H., Itesako, T., Kojima, S., Kinoshita, T., Tatarano, S., et al. (2013). Tumor-suppressive microRNA-143/145 cluster targets hexokinase-2 in renal cell carcinoma. Cancer Sci, 104(12), 1567–1574.PubMedCrossRef
67.
Kojima, S., Enokida, H., Yoshino, H., Itesako, T., Chiyomaru, T., Kinoshita, T., et al. (2014). The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer. J Hum Genet, 59(2), 78–87.PubMedCrossRef
68.
Shao, Y., Qu, Y., Dang, S., Yao, B., & Ji, M. (2013). MiR-145 inhibits oral squamous cell carcinoma (OSCC) cell growth by targeting c-Myc and Cdk6. Cancer Cell Int, 13(1), 51.PubMedPubMedCentralCrossRef
69.
Liu, R., Liao, J., Yang, M., Sheng, J., Yang, H., Wang, Y., et al. (2012). The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1. PLoS One, 7(3), e33987.PubMedPubMedCentralCrossRef
70.
Zhang, J., Sun, Q., Zhang, Z., Ge, S., Han, Z. G., & Chen, W. T. (2013). Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop. Oncogene, 32(1), 61–69.PubMedCrossRef
71.
Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., et al. (2009). p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A, 106(9), 3207–3212.PubMedPubMedCentralCrossRef
72.
Suzuki, H. I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009). Modulation of microRNA processing by p53. Nature, 460(7254), 529–533.PubMedCrossRef
73.
Chen, Z., Zeng, H., Guo, Y., Liu, P., Pan, H., Deng, A., et al. (2010). miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Exp Clin Cancer Res, 29, 151.
74.
Vogelstein, B., Lane, D., & Levine, A. J. (2000). Surfing the p53 network. Nature, 408(6810), 307–310.PubMedCrossRef
75.
Guimaraes, D. P., & Hainaut, P. (2002). TP53: a key gene in human cancer. Biochimie, 84(1), 83–93.PubMedCrossRef
76.
Kumar, M., Lu, Z., Takwi, A. A., Chen, W., Callander, N. S., Ramos, K. S., et al. (2011). Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene, 30(7), 843–853.PubMedCrossRef
77.
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature, 447(7148), 1130–1134.PubMedPubMedCentralCrossRef
78.
Rokavec, M., Li, H., Jiang, L., & Hermeking, H. (2014). The p53/microRNA connection in gastrointestinal cancer. Clin Exp Gastroenterol, 7, 395–413.PubMedPubMedCentral
79.
Zhang, D. G., Zheng, J. N., & Pei, D. S. (2014). P53/microRNA-34-induced metabolic regulation: new opportunities in anticancer therapy. Mol Cancer, 13, 115.PubMedPubMedCentralCrossRef
80.
Chang, T. C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., et al. (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell, 26(5), 745–752.PubMedPubMedCentralCrossRef
81.
Kumar, B., Yadav, A., Lang, J., Teknos, T. N., & Kumar, P. (2012). Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS One, 7(5), e37601.PubMedPubMedCentralCrossRef
82.
Jiang, H., Zhang, G., Wu, J. H., & Jiang, C. P. (2014). Diverse roles of miR-29 in cancer (review). Oncol Rep, 31(4), 1509–1516.PubMedCrossRef
83.
Kinoshita, T., Nohata, N., Hanazawa, T., Kikkawa, N., Yamamoto, N., Yoshino, H., et al. (2013). Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma. Br J Cancer, 109(10), 2636–2645.PubMedPubMedCentralCrossRef
84.
Nishikawa, R., Chiyomaru, T., Enokida, H., Inoguchi, S., Ishihara, T., Matsushita, R., et al. (2015). Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma. FEBS Lett, 589(16), 2136–2145.PubMedCrossRef
85.
Nishikawa, R., Goto, Y., Kojima, S., Enokida, H., Chiyomaru, T., Kinoshita, T., et al. (2014). Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol, 45(1), 401–410.PubMedCrossRef
86.
Yamamoto, N., Kinoshita, T., Nohata, N., Yoshino, H., Itesako, T., Fujimura, L., et al. (2013). Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma. Int J Oncol, 43(6), 1855–1863.PubMedPubMedCentralCrossRef
87.
Kamikawaji, K., Seki, N., Watanabe, M., Mataki, H., Kumamoto, T., Takagi, K., et al. (2016). Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis. J Hum Genet, 61(12), 985–993.PubMedCrossRef
88.
Wang, Y., Zhang, X., Li, H., Yu, J., & Ren, X. (2013). The role of miRNA-29 family in cancer. Eur J Cell Biol, 92(3), 123–128.PubMedCrossRef
89.
Melo, S. A., & Kalluri, R. (2013). miR-29b moulds the tumour microenvironment to repress metastasis. Nat Cell Biol, 15(2), 139–140.PubMedCrossRef
90.
91.
Fuse, M., Kojima, S., Enokida, H., Chiyomaru, T., Yoshino, H., Nohata, N., et al. (2012). Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer. J Hum Genet, 57(11), 691–699.PubMedCrossRef
92.
Fukumoto, I., Kikkawa, N., Matsushita, R., Kato, M., Kurozumi, A., Nishikawa, R., et al. (2016). Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma. J Hum Genet, 61(2), 109–118.PubMedCrossRef
93.
Yu, L., Lu, J., Zhang, B., Liu, X., Wang, L., Li, S. Y., et al. (2013). miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2. Oncol Lett, 5(4), 1223–1228.PubMedPubMedCentral
94.
Lu, J., He, M. L., Wang, L., Chen, Y., Liu, X., Dong, Q., et al. (2011). MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res, 71(1), 225–233.PubMedCrossRef
95.
Koh, C. M., Iwata, T., Zheng, Q., Bethel, C., Yegnasubramanian, S., & De Marzo, A. M. (2011). Myc enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and post-transcriptional mechanisms. Oncotarget, 2(9), 669–683.PubMedPubMedCentralCrossRef
96.
Kurozumi, A., Kato, M., Goto, Y., Matsushita, R., Nishikawa, R., Okato, A., et al. (2016). Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. Int J Oncol, 48(5), 1837–1846.PubMedPubMedCentralCrossRef
97.
Miyamoto, K., Seki, N., Matsushita, R., Yonemori, M., Yoshino, H., Nakagawa, M., et al. (2016). Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer. Br J Cancer, 115, 354–363.PubMedPubMedCentralCrossRef
98.
Kano, M., Seki, N., Kikkawa, N., Fujimura, L., Hoshino, I., Akutsu, Y., et al. (2010). miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer, 127(12), 2804–2814.PubMedCrossRef
99.
Nohata, N., Hanazawa, T., Kikkawa, N., Mutallip, M., Sakurai, D., Fujimura, L., et al. (2011). Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC). J Hum Genet, 56(8), 595–601.PubMedCrossRef
100.
Yan, J. W., Lin, J. S., & He, X. X. (2014). The emerging role of miR-375 in cancer. Int J Cancer, 135(5), 1011–1018.PubMedCrossRef
101.
Wei, R., Yang, Q., Han, B., Li, Y., Yao, K., Yang, X., et al. (2017). microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways. Oncotarget, 8(10), 16633-16641.
102.
Ding, L., Xu, Y., Zhang, W., Deng, Y., Si, M., Du, Y., et al. (2010). MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res, 20(7), 784–793.PubMedCrossRef
103.
Pfeffer, S. R., Yang, C. H., & Pfeffer, L. M. (2015). The Role of miR-21 in cancer. Drug Dev Res, 76(6), 270–277.PubMedCrossRef
104.
Ren, J., Zhu, D., Liu, M., Sun, Y., & Tian, L. (2010). Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of laryngeal squamous cell carcinoma. Eur J Cancer, 46(18), 3409–3416.PubMedCrossRef
105.
Fu, X., Han, Y., Wu, Y., Zhu, X., Lu, X., Mao, F., et al. (2011). Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis. Eur J Clin Invest, 41(11), 1245–1253.PubMedCrossRef
106.
Mace, T. A., Collins, A. L., Wojcik, S. E., Croce, C. M., Lesinski, G. B., & Bloomston, M. (2013). Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res, 184(2), 855–860.PubMedPubMedCentralCrossRef
107.
Li, L., Li, C., Wang, S., Wang, Z., Jiang, J., Wang, W., et al. (2016). Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype. Cancer Res, 76(7), 1770–1780.PubMedCrossRef
108.
Dambal, S., Shah, M., Mihelich, B., & Nonn, L. (2015). The microRNA-183 cluster: the family that plays together stays together. Nucleic Acids Res, 43(15), 7173–7188.PubMedPubMedCentralCrossRef
109.
Zhang, Q. H., Sun, H. M., Zheng, R. Z., Li, Y. C., Zhang, Q., Cheng, P., et al. (2013). Meta-analysis of microRNA-183 family expression in human cancer studies comparing cancer tissues with noncancerous tissues. Gene, 527(1), 26–32.PubMedCrossRef
110.
Ma, Y., Liang, A. J., Fan, Y. P., Huang, Y. R., Zhao, X. M., Sun, Y., et al. (2016). Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis. Oncotarget, 7(27), 42805–42825.PubMedPubMedCentralCrossRef
111.
Wang, L., Jiang, H., Li, W., Jia, C., Zhang, H., Sun, Y., et al. (2017). Overexpression of TP53 mutation-associated microRNA-182 promotes tumor cell proliferation and migration in head and neck squamous cell carcinoma. Arch Oral Biol, 73, 105–112.PubMedCrossRef
112.
113.
114.
Jones, P. A., & Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nat Rev Genet, 3(6), 415–428.PubMed
115.
Lujambio, A., Ropero, S., Ballestar, E., Fraga, M. F., Cerrato, C., Setien, F., et al. (2007). Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res, 67(4), 1424–1429.PubMedCrossRef
116.
Chuang, J. C., & Jones, P. A. (2007). Epigenetics and microRNAs. Pediatr Res, 61(5 Pt 2), 24r–29r.PubMedCrossRef
117.
Guil, S., & Esteller, M. (2009). DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol, 41(1), 87–95.PubMedCrossRef
118.
Iorio, M. V., Piovan, C., & Croce, C. M. (2010). Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta, 1799(10–12), 694–701.PubMedCrossRef
119.
Egger, G., Liang, G., Aparicio, A., & Jones, P. A. (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429(6990), 457–463.PubMedCrossRef
120.
Klose, R. J., & Bird, A. P. (2006). Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci, 31(2), 89–97.PubMedCrossRef
121.
Kozaki, K., & Inazawa, J. (2012). Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells. Cancer Sci, 103(5), 837–845.PubMedCrossRef
122.
Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., et al. (2007). MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A, 104(40), 15805–15810.PubMedPubMedCentralCrossRef
123.
Xu, H., Sun, J., Shi, C., Sun, C., Yu, L., Wen, Y., et al. (2015). miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B. Neurosci Lett, 590, 40–46.PubMedCrossRef
124.
Solly, F., Koering, C., Mint-Mohamed, A., Maucort-Boulch, D., Robert, G., Auberger, P., et al. (2017). A miRNAs-DNMT1 axis is involved in azacitidine-resistance and predicts survival in higher risk myelodysplastic syndrome and low blast count acute myeloid leukemia. Clin Cancer Res, 23(12), 3025-3034
125.
Fraga, M. F., & Esteller, M. (2005). Towards the human cancer epigenome: a first draft of histone modifications. Cell Cycle, 4(10), 1377–1381.PubMedCrossRef
126.
Yang, X. J., & Seto, E. (2007). HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene, 26(37), 5310–5318.PubMedCrossRef
127.
Sampath, D., Liu, C., Vasan, K., Sulda, M., Puduvalli, V. K., Wierda, W. G., et al. (2012). Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. Blood, 119(5), 1162–1172.PubMedPubMedCentralCrossRef
128.
Kim, H. S., Shen, Q., & Nam, S. W. (2015). Histone deacetylases and their regulatory microRNAs in hepatocarcinogenesis. J Korean Med Sci, 30(10), 1375–1380.PubMedPubMedCentralCrossRef
129.
Scott, G. K., Mattie, M. D., Berger, C. E., Benz, S. C., & Benz, C. C. (2006). Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res, 66(3), 1277–1281.PubMedCrossRef
130.
Chase, A., & Cross, N. C. (2011). Aberrations of EZH2 in cancer. Clin Cancer Res, 17(9), 2613–2618.PubMedCrossRef
131.
Sun, S., Yu, F., Zhang, L., & Zhou, X. (2016). EZH2, an on-off valve in signal network of tumor cells. Cell Signal, 28(5), 481–487.PubMedCrossRef
132.
Tsang, D. P., & Cheng, A. S. (2011). Epigenetic regulation of signaling pathways in cancer: role of the histone methyltransferase EZH2. J Gastroenterol Hepatol, 26(1), 19–27.PubMedCrossRef
133.
134.
Goto, Y., Kurozumi, A., Nohata, N., Kojima, S., Matsushita, R., Yoshino, H., et al. (2016). The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma. Oncotarget. doi:10.​18632/​oncotarget.​10887.
135.
Wang, H., Meng, Y., Cui, Q., Qin, F., Yang, H., Chen, Y., et al. (2016). MiR-101 targets the EZH2/Wnt/beta-catenin the pathway to promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Sci Rep, 6, 36988.PubMedPubMedCentralCrossRef
136.
Konno, Y., Dong, P., Xiong, Y., Suzuki, F., Lu, J., Cai, M., et al. (2014). MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells. Oncotarget, 5(15), 6049–6062.PubMedPubMedCentralCrossRef
137.
Zhang, K., Zhang, Y., Ren, K., Zhao, G., Yan, K., & Ma, B. (2014). MicroRNA-101 inhibits the metastasis of osteosarcoma cells by downregulation of EZH2 expression. Oncol Rep, 32(5), 2143–2149.PubMedCrossRef
138.
Wang, H. J., Ruan, H. J., He, X. J., Ma, Y. Y., Jiang, X. T., Xia, Y. J., et al. (2010). MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer, 46(12), 2295–2303.PubMedCrossRef
139.
Zhang, B., Liu, X. X., He, J. R., Zhou, C. X., Guo, M., He, M., et al. (2011). Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis, 32(1), 2–9.PubMedCrossRef
140.
Kato, M., Kurozumi, A., Goto, Y., Matsushita, R., Okato, A., Nishikawa, R., et al. (2017). Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer. J Hum Genet, 62(1), 123–132.PubMedCrossRef
141.
Bronner, C., Krifa, M., & Mousli, M. (2013). Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as well as in tumorogenesis. Biochem Pharmacol, 86(12), 1643–1649.PubMedCrossRef
142.
143.
Thiery, J. P. (2002). Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2(6), 442–454.PubMedCrossRef
144.
145.
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., et al. (2005). RAS is regulated by the let-7 microRNA family. Cell, 120(5), 635–647.PubMedCrossRef
146.
Lamouille, S., Subramanyam, D., Blelloch, R., & Derynck, R. (2013). Regulation of epithelial-mesenchymal and mesenchymal-epithelial transitions by microRNAs. Curr Opin Cell Biol, 25(2), 200–207.PubMedPubMedCentralCrossRef
147.
Bracken, C. P., Gregory, P. A., Khew-Goodall, Y., & Goodall, G. J. (2009). The role of microRNAs in metastasis and epithelial-mesenchymal transition. Cell Mol Life Sci, 66(10), 1682–1699.PubMedCrossRef
148.
Spoelstra, N. S., Manning, N. G., Higashi, Y., Darling, D., Singh, M., Shroyer, K. R., et al. (2006). The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers. Cancer Res, 66(7), 3893–3902.PubMedCrossRef
149.
150.
Sekhon, K., Bucay, N., Majid, S., Dahiya, R., & Saini, S. (2016). MicroRNAs and epithelial-mesenchymal transition in prostate cancer. Oncotarget, 7(41), 67597–67611.PubMedPubMedCentralCrossRef
151.
152.
153.
Feng, X., Wang, Z., Fillmore, R., & Xi, Y. (2014). MiR-200, a new star miRNA in human cancer. Cancer Lett, 344(2), 166–173.PubMedCrossRef
154.
Hill, L., Browne, G., & Tulchinsky, E. (2013). ZEB/miR-200 feedback loop: at the crossroads of signal transduction in cancer. Int J Cancer, 132(4), 745–754.PubMedCrossRef
155.
Korpal, M., & Kang, Y. (2008). The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol, 5(3), 115–119.PubMedPubMedCentralCrossRef
156.
Kim, T., Veronese, A., Pichiorri, F., Lee, T. J., Jeon, Y. J., Volinia, S., et al. (2011). p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med, 208(5), 875–883.PubMedPubMedCentralCrossRef
157.
Liu, Y. N., Yin, J. J., Abou-Kheir, W., Hynes, P. G., Casey, O. M., Fang, L., et al. (2013). MiR-1 and miR-200 inhibit EMT via slug-dependent and tumorigenesis via slug-independent mechanisms. Oncogene, 32(3), 296–306.PubMedCrossRef
158.
Chang, Y. S., Chen, W. Y., Yin, J. J., Sheppard-Tillman, H., Huang, J., & Liu, Y. N. (2015). EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1. Cancer Res, 75(15), 3077–3086.PubMedPubMedCentralCrossRef
159.
Peng, X., Guo, W., Liu, T., Wang, X., Tu, X., Xiong, D., et al. (2011). Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One, 6(5), e20341.PubMedPubMedCentralCrossRef
160.
Ren, D., Wang, M., Guo, W., Huang, S., Wang, Z., Zhao, X., et al. (2014). Double-negative feedback loop between ZEB2 and miR-145 regulates epithelial-mesenchymal transition and stem cell properties in prostate cancer cells. Cell Tissue Res, 358(3), 763–778.PubMedCrossRef
161.
Kinoshita, T., Hanazawa, T., Nohata, N., Kikkawa, N., Enokida, H., Yoshino, H., et al. (2012). Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma. Oncotarget, 3(11), 1386–1400.PubMedPubMedCentralCrossRef
162.
Mizuno, K., Seki, N., Mataki, H., Matsushita, R., Kamikawaji, K., Kumamoto, T., et al. (2016). Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. Int J Oncol, 48(2), 450–460.PubMedCrossRef
163.
Wu, L., & Zhu, Y. (2015). The function and mechanisms of action of LOXL2 in cancer (Review). Int J Mol Med, 36(5), 1200–1204.PubMedCrossRef
164.
Moon, H. J., Finney, J., Ronnebaum, T., & Mure, M. (2014). Human lysyl oxidase-like 2. Bioorg Chem, 57, 231–241.PubMedCrossRef
165.
Schietke, R., Warnecke, C., Wacker, I., Schodel, J., Mole, D. R., Campean, V., et al. (2010). The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1. J Biol Chem, 285(9), 6658–6669.PubMedCrossRef
166.
Millanes-Romero, A., Herranz, N., Perrera, V., Iturbide, A., Loubat-Casanovas, J., Gil, J., et al. (2013). Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition. Mol Cell, 52(5), 746–757.PubMedCrossRef
167.
Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J. J., & Lotvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 9(6), 654–659.PubMedCrossRef
168.
Kinoshita, T., Yip, K. W., Spence, T., & Liu, F. F. (2017). MicroRNAs in extracellular vesicles: potential cancer biomarkers. J Hum Genet, 62(1), 67–74.PubMedCrossRef
169.
Chen, X., Ba, Y., Ma, L., Cai, X., Yin, Y., Wang, K., et al. (2008). Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res, 18(10), 997–1006.PubMedCrossRef
170.
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A, 105(30), 10513–10518.PubMedPubMedCentralCrossRef
171.
Liu, Q., Yu, Z., Yuan, S., Xie, W., Li, C., Hu, Z., et al. (2016). Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget. doi:10.​18632/​oncotarget.​14369.
172.
Halvorsen, A. R., Helland, A., Gromov, P., Wielenga, V. T., Talman, M. M., Brunner, N., et al. (2017). Profiling of microRNAs in tumor interstitial fluid of breast tumors—a novel resource to identify biomarkers for prognostic classification and detection of cancer. Mol Oncol, 11(2), 220–234.PubMedCrossRef
173.
Foj, L., Ferrer, F., Serra, M., Arevalo, A., Gavagnach, M., Gimenez, N., et al. (2016). Exosomal and non-exosomal urinary miRNAs in prostate cancer detection and prognosis. Prostate, 77(6), 573–583.PubMedCrossRef
174.
Pei, Z., Liu, S. M., Huang, J. T., Zhang, X., Yan, D., Xia, Q., et al. (2017). Clinically relevant circulating microRNA profiling studies in pancreatic cancer using meta-analysis. Oncotarget, 8(14), 22616–22624.PubMedPubMedCentral
175.
Hsu, C. M., Lin, P. M., Wang, Y. M., Chen, Z. J., Lin, S. F., & Yang, M. Y. (2012). Circulating miRNA is a novel marker for head and neck squamous cell carcinoma. Tumour Biol, 33(6), 1933–1942.PubMedCrossRef
176.
Hou, B., Ishinaga, H., Midorikawa, K., Shah, S. A., Nakamura, S., Hiraku, Y., et al. (2015). Circulating microRNAs as novel prognosis biomarkers for head and neck squamous cell carcinoma. Cancer Biol Ther, 16(7), 1042–1046.PubMedPubMedCentralCrossRef
177.
Summerer, I., Unger, K., Braselmann, H., Schuettrumpf, L., Maihoefer, C., Baumeister, P., et al. (2015). Circulating microRNAs as prognostic therapy biomarkers in head and neck cancer patients. Br J Cancer, 113(1), 76–82.PubMedPubMedCentralCrossRef
Metadata
Title
Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma
Authors
Keiichi Koshizuka
Toyoyuki Hanazawa
Takayuki Arai
Atsushi Okato
Naoko Kikkawa
Naohiko Seki
Publication date
01-09-2017
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 3/2017
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-017-9692-y

Other articles of this Issue 3/2017

Cancer and Metastasis Reviews 3/2017 Go to the issue

OriginalPaper

mTOR co-targeting strategies for head and neck cancer therapy

OriginalPaper

Targeting metabolic pathways for head and neck cancers therapeutics

OriginalPaper

Tumor DNA: an emerging biomarker in head and neck cancer

OriginalPaper

Alcohol and head and neck cancer

OriginalPaper

Tobacco-related carcinogenesis in head and neck cancer

OriginalPaper

EGFR-targeted therapies in the post-genomic era
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits