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
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Colorectal Cancer | Review

Emerging role of non-coding RNAs in the regulation of KRAS

Authors: Soudeh Ghafouri-Fard, Zeinab Shirvani-Farsani, Bashdar Mahmud Hussen, Mohammad Taheri, Reza Jalili Khoshnoud

Published in: Cancer Cell International | Issue 1/2022

Login to get access

Abstract

The Kirsten ras oncogene KRAS is a member of the small GTPase superfamily participating in the RAS/MAPK pathway. A single amino acid substitution in KRAS gene has been shown to activate the encoded protein resulting in cell transformation. This oncogene is involved in the malignant transformation in several tissues. Notably, numerous non-coding RNAs have been found to interact with KRAS protein. Such interaction results in a wide array of human disorders, particularly cancers. Orilnc1, KIMAT1, SLCO4A1-AS1, LINC01420, KRAS1P, YWHAE, PART1, MALAT1, PCAT-1, lncRNA-NUTF2P3-001 and TP53TG1 are long non-coding RNAs (lncRNAs) whose interactions with KRAS have been verified in the context of cancer. miR-143, miR-96, miR-134 and miR-126 have also been shown to interact with KRAS in different tissues. Finally, circITGA7, circ_GLG1, circFNTA and circ-MEMO1 are examples of circular RNAs (circRNAs) that interact with KRAS. In this review, we describe the interaction between KRAS and lncRNAs, miRNAs and circRNAs, particularly in the context of cancer.
Literature
1.
Chang EH, Gonda MA, Ellis RW, Scolnick EM, Lowy DR. Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses. Proc Natl Acad Sci. 1982;79(16):4848–52.PubMedPubMedCentral
2.
McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Goeddel DV, et al. Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983;304(5926):501–6.PubMed
3.
Giglione C, Parrini MC, Baouz S, Bernardi A, Parmeggiani A. A new function of p120-GTPase-activating protein. J Biol Chem. 1997;272(40):25128–34.PubMed
4.
Der CJ, Cooper GM. Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas. Cell. 1983;32(1):201–8.PubMed
5.
6.
Ward AF, Braun BS, Shannon KM. Targeting oncogenic Ras signaling in hematologic malignancies. Blood J Am Soc Hematol. 2012;120(17):3397–406.
7.
Zhao S, Zhang Y, Sha K, Tang Q, Yang X, Yu C, et al. KRAS (G12D) cooperates with AML1/ETO to initiate a mouse model mimicking human acute myeloid leukemia. Cell Physiol Biochem. 2014;33(1):78–87.PubMed
8.
Zhou J-D, Yao D-M, Li X-X, Zhang T-J, Zhang W, Ma J-C, et al. KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia. Oncotarget. 2017;8(39):66087.PubMedPubMedCentral
9.
10.
Mustachio LM, Chelariu-Raicu A, Szekvolgyi L, Roszik J. Targeting KRAS in cancer: promising therapeutic strategies. Cancers. 2021;13(6):1204.PubMedPubMedCentral
11.
12.
Zhang X, Wang W, Zhu W, Dong J, Cheng Y, Yin Z, et al. Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int J Mol Sci. 2019;20(22):5573.PubMedCentral
13.
Kuo CC, Hänzelmann S, Sentürk Cetin N, Frank S, Zajzon B, Derks JP, et al. Detection of RNA-DNA binding sites in long noncoding RNAs. Nucleic Acids Res. 2019;47(6):e32 (Epub 2019/01/31).PubMedPubMedCentral
14.
Zhang D, Zhang G, Hu X, Wu L, Feng Y, He S, et al. Oncogenic RAS regulates long noncoding RNA Orilnc1 in human cancer. Cancer Res. 2017;77(14):3745–57 (Epub 05/04).PubMedPubMedCentral
15.
Shi L, Magee P, Fassan M, Sahoo S, Leong HS, Lee D, et al. A KRAS-responsive long non-coding RNA controls microRNA processing. Nat Commun. 2021;12(1):2038.PubMedPubMedCentral
16.
Tang R, Chen J, Tang M, Liao Z, Zhou L, Jiang J, et al. LncRNA SLCO4A1-AS1 predicts poor prognosis and promotes proliferation and metastasis via the EGFR/MAPK pathway in colorectal cancer. Int J Biol Sci. 2019;15(13):2885–96.PubMedPubMedCentral
17.
Zhai H, Zhang X, Sun X, Zhang D, Ma S. Long non-coding RNA LINC01420 contributes to pancreatic cancer progression through targeting KRAS proto-oncogene. Dig Dis Sci. 2020;65(4):1042–52.PubMed
18.
Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465(7301):1033–8.PubMedPubMedCentral
19.
Bjeije H, Soltani BM, Behmanesh M, Zali MR. YWHAE long non-coding RNA competes with miR-323a-3p and miR-532-5p through activating K-Ras/Erk1/2 and PI3K/Akt signaling pathways in HCT116 cells. Hum Mol Genet. 2019;28(19):3219–31.PubMed
20.
Chen SC, Diao YZ, Zhao ZH, Li XL. Inhibition of lncRNA PART1 chemosensitizes wild type but Not KRAS mutant NSCLC cells. Cancer Manag Res. 2020;12:4453–60 (Epub 2020/07/02).PubMedPubMedCentral
21.
Chang J, Xu W, Du X, Hou J. MALAT1 silencing suppresses prostate cancer progression by upregulating miR-1 and downregulating KRAS. Onco Targets Ther. 2018;11:3461–73.PubMedPubMedCentral
22.
Domvri K, Petanidis S, Anestakis D, Porpodis K, Bai C, Zarogoulidis P, et al. Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance via immunosuppressive miR-182/miR-217 signaling and p27/CDK6 regulation. Oncotarget. 2020;11(29):2847.PubMedPubMedCentral
23.
Li X, Deng S-J, Zhu S, Jin Y, Cui S-P, Chen J-Y, et al. Hypoxia-induced lncRNA-NUTF2P3-001 contributes to tumorigenesis of pancreatic cancer by derepressing the miR-3923/KRAS pathway. Oncotarget. 2016;7(5):6000–14.PubMedPubMedCentral
24.
Zhang Y, Yang H, Du Y, Liu P, Zhang J, Li Y, et al. Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA-96. Cancer Sci. 2019;110(9):2760–72.PubMedPubMedCentral
25.
Macfarlane L-A, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genom. 2010;11(7):537–61.
26.
Zhao W-G, Yu S-N, Lu Z-H, Ma Y-H, Gu Y-M, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010;31(10):1726–33.PubMed
27.
Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010;70(14):6015–25.PubMed
28.
Tanaka M, Suzuki HI, Shibahara J, Kunita A, Isagawa T, Yoshimi A, et al. EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis. Oncogene. 2014;33(19):2454–63.PubMed
29.
Saud SM, Li W, Morris NL, Matter MS, Colburn NH, Kim YS, et al. Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression. Carcinogenesis. 2014;35(12):2778–86 (Epub 10/03).PubMedPubMedCentral
30.
Milanesi E, Dobre M, Bucuroiu AI, Herlea V, Manuc TE, Salvi A, et al. miRNAs-based molecular signature for KRAS mutated and wild type colorectal cancer: an explorative study. J Immunol Res. 2020;2020:4927120.PubMedPubMedCentral
31.
Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y, et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009;28(10):1385–92.PubMed
32.
Xie F, Li C, Zhang X, Peng W, Wen T. MiR-143-3p suppresses tumorigenesis in pancreatic ductal adenocarcinoma by targeting KRAS. Biomed Pharmacother. 2019;119: 109424.PubMed
33.
Pichler M, Winter E, Stotz M, Eberhard K, Samonigg H, Lax S, et al. Down-regulation of KRAS-interacting miRNA-143 predicts poor prognosis but not response to EGFR-targeted agents in colorectal cancer. Br J Cancer. 2012;106(11):1826–32 (Epub 05/01).PubMedPubMedCentral
34.
Akao Y, Kumazaki M, Shinohara H, Sugito N, Kuranaga Y, Tsujino T, et al. Impairment of K-Ras signaling networks and increased efficacy of epidermal growth factor receptor inhibitors by a novel synthetic miR-143. Cancer Sci. 2018;109(5):1455–67 (Epub 04/14).PubMedPubMedCentral
35.
Xu B, Niu X, Zhang X, Tao J, Wu D, Wang Z, et al. miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem. 2011;350(1):207–13.PubMed
36.
Kang M, Li Y, Zhu S, Zhang S, Guo S, Li P. MicroRNA-193b acts as a tumor suppressor gene in human esophageal squamous cell carcinoma via target regulation of KRAS. Oncol Lett. 2019;17(4):3965–73.PubMedPubMedCentral
37.
Mokhlis HA, Bayraktar R, Kabil NN, Caner A, Kahraman N, Rodriguez-Aguayo C, et al. The modulatory role of microRNA-873 in the progression of KRAS-driven cancers. Mole Ther Nucleic Acids. 2019;14:301–17 (Epub 2019/01/18).
38.
Lundberg IV, Wikberg ML, Ljuslinder I, Li X, Myte R, Zingmark C, et al. MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers. Anticancer Res. 2018;38(2):677–83.PubMed
39.
Shi L, Middleton J, Jeon Y-J, Magee P, Veneziano D, Laganà A, et al. KRAS induces lung tumorigenesis through microRNAs modulation. Cell Death Dis. 2018;9(2):219.PubMedPubMedCentral
40.
Shen H, Xing C, Cui K, Li Y, Zhang J, Du R, et al. MicroRNA-30a attenuates mutant KRAS-driven colorectal tumorigenesis via direct suppression of ME1. Cell Death Differ. 2017;24(7):1253–62.PubMedPubMedCentral
41.
Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008;68(20):8535–40.PubMedPubMedCentral
42.
Mosakhani N, Sarhadi VK, Borze I, Karjalainen-Lindsberg M-L, Sundström J, Ristamäki R, et al. MicroRNA profiling differentiates colorectal cancer according to KRAS status. Genes Chromosom Cancer. 2012;51(1):1–9.PubMed
43.
Tsang WP, Kwok TT. The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras. Carcinogenesis. 2009;30(6):953–9.PubMed
44.
Pugh S, Thiébaut R, Bridgewater J, Grisoni M-L, Moutasim K, Rousseau F, et al. Association between miR-31-3p expression and cetuximab efficacy in patients with KRAS wild-type metastatic colorectal cancer: a post-hoc analysis of the new EPOC trial. Oncotarget. 2017;8(55):93856–66.PubMedPubMedCentral
45.
Kent OA, Mendell JT, Rottapel R. Transcriptional regulation of miR-31 by oncogenic KRAS mediates metastatic phenotypes by repressing RASA1. Mol Cancer Res. 2016;14(3):267–77 (Epub 01/08).PubMedPubMedCentral
46.
Forzati F, De Martino M, Esposito F, Sepe R, Pellecchia S, Malapelle U, et al. miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene. BMC Cancer. 2017;17(1):170.PubMedPubMedCentral
47.
Fan Q, Hu X, Zhang H, Wang S, Zhang H, You C, et al. MiR-193a-3p is an important tumour suppressor in lung cancer and directly targets KRAS. Cell Physiol Biochem. 2017;44(4):1311–24.PubMed
48.
Tsunoda T, Takashima Y, Yoshida Y, Doi K, Tanaka Y, Fujimoto T, et al. Oncogenic KRAS regulates miR-200c and miR-221/222 in a 3D-specific manner in colorectal cancer cells. Anticancer Res. 2011;31(7):2453–9.PubMed
49.
Inoue A, Mizushima T, Wu X, Okuzaki D, Kambara N, Ishikawa S, et al. A miR-29b byproduct sequence exhibits potent tumor-suppressive activities via inhibition of NF-κB signaling in KRAS-mutant colon cancer cells. Mol Cancer Ther. 2018;17(5):977–87.PubMed
50.
Hara T, Jones MF, Subramanian M, Li XL, Ou O, Zhu Y, et al. Selective targeting of KRAS-mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-mutant cells. Oncotarget. 2014;5(17):7635–50.PubMedPubMedCentral
51.
Fiala O, Pitule P, Hosek P, Liska V, Sorejs O, Bruha J, et al. The association of miR-126-3p, miR-126-5p and miR-664-3p expression profiles with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. Tumor Biol. 2017;39(7):1010428317709283.
52.
Ebrahimi F, Gopalan V, Wahab R, Lu C-T, Anthony Smith R, Lam AK-Y. Deregulation of miR-126 expression in colorectal cancer pathogenesis and its clinical significance. Exp Cell Res. 2015;339(2):333–41.PubMed
53.
Mamoori A, Wahab R, Islam F, Lee K, Vider J, Lu C-T, et al. Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis. Hum Pathol. 2018;71:145–56.PubMed
54.
Ota T, Doi K, Fujimoto T, Tanaka Y, Ogawa M, Matsuzaki H, et al. KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells. Anticancer Res. 2012;32(6):2271–5.PubMed
55.
Zhang Y, Kim J, Mueller AC, Dey B, Yang Y, Lee DH, et al. Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma. Cell Death Differ. 2014;21(5):720–34.PubMedPubMedCentral
56.
Liu Y, Zhang M, Qian J, Bao M, Meng X, Zhang S, et al. miR-134 functions as a tumor suppressor in cell proliferation and epithelial-to-mesenchymal transition by targeting KRAS in renal cell carcinoma cells. DNA Cell Biol. 2015;34(6):429–36 (Epub 03/26).PubMedPubMedCentral
57.
Zhao Y, Pang D, Wang C, Zhong S, Wang S. MicroRNA-134 modulates glioma cell U251 proliferation and invasion by targeting KRAS and suppressing the ERK pathway. Tumor Biol. 2016;37(8):11485–93.
58.
Guo L, Bai Y, Ji S, Ma H. MicroRNA-98 suppresses cell growth and invasion of retinoblastoma via targeting the IGF1R/k-Ras/Raf/MEK/ERK signaling pathway. Int J Oncol. 2019;54(3):807–20.PubMedPubMedCentral
59.
Ruzzo A, Graziano F, Vincenzi B, Canestrari E, Perrone G, Galluccio N, et al. High let-7a microRNA levels in KRAS-mutated colorectal carcinomas may rescue anti-EGFR therapy effects in patients with chemotherapy-refractory metastatic disease. Oncologist. 2012;17(6):823–9 (Epub 05/14).PubMedPubMedCentral
60.
Jin X, Sun Y, Yang H, Li J, Yu S, Chang X, et al. Deregulation of the MiR-193b-KRAS axis contributes to impaired cell growth in pancreatic cancer. PLoS ONE. 2015;10(4): e0125515.PubMedPubMedCentral
61.
Keklikoglou I, Hosaka K, Bender C, Bott A, Koerner C, Mitra D, et al. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Oncogene. 2015;34(37):4867–78.PubMed
62.
Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, et al. Modulation of K-Ras-dependent lung tumorigenesis by microRNA-21. Cancer Cell. 2010;18(3):282–93.PubMedPubMedCentral
63.
Yuan P, He X-H, Rong Y-F, Cao J, Li Y, Hu Y-P, et al. KRAS/NF-κB/YY1/miR-489 signaling axis controls pancreatic cancer metastasis. Cancer Res. 2017;77(1):100–11.PubMed
64.
Wang P, Zhu C-F, Ma M-Z, Chen G, Song M, Zeng Z-L, et al. Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer. Oncotarget. 2015;6(25):21148–58.PubMedPubMedCentral
65.
Liu X, Wang Y, Zhao J. MicroRNA-337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways. Oncol Rep. 2017;38(5):3187–96.PubMed
66.
Zhang X, Guo Q, Chen J, Chen Z. Quercetin enhances cisplatin sensitivity of human osteosarcoma cells by modulating microRNA-217-KRAS axis. Mol Cells. 2015;38(7):638–42 (Epub 06/10).PubMedPubMedCentral
67.
Seviour EG, Sehgal V, Mishra D, Rupaimoole R, Rodriguez-Aguayo C, Lopez-Berestein G, et al. Targeting KRas-dependent tumour growth, circulating tumour cells and metastasis in vivo by clinically significant miR-193a-3p. Oncogene. 2017;36(10):1339–50 (Epub 09/26).PubMed
68.
Subramani A, Alsidawi S, Jagannathan S, Sumita K, Sasaki AT, Aronow B, et al. The brain microenvironment negatively regulates miRNA-768-3p to promote K-ras expression and lung cancer metastasis. Sci Rep. 2013;3(1):2392.PubMedPubMedCentral
69.
Sayed D, Hong C, Chen I-Y, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007;100(3):416–24.PubMed
70.
Zhao X, Cai Y, Xu J. Circular RNAs: biogenesis, mechanism, and function in human cancers. Int J Mol Sci. 2019;20(16):3926.PubMedCentral
71.
Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–57.PubMedPubMedCentral
72.
Hao S, Qu R, Hu C, Wang M, Li Y. A circular RNA derived from golgi glycoprotein 1 mRNA regulates KRAS expression and promotes colorectal cancer progression by targeting microRNA-622. Onco Targets Ther. 2020;13:12637–48 (Epub 2020/12/19).PubMedPubMedCentral
73.
Li X, Wang J, Zhang C, Lin C, Zhang J, Zhang W, et al. Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7. J Pathol. 2018;246(2):166–79.PubMed
74.
Dou Y, Cha DJ, Franklin JL, Higginbotham JN, Jeppesen DK, Weaver AM, et al. Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes. Sci Rep. 2016;6(1):37982.PubMedPubMedCentral
75.
Chen J, Sun Y, Ou Z, Yeh S, Huang C-P, You B, et al. Androgen receptor-regulated circFNTA activates KRAS signaling to promote bladder cancer invasion. EMBO Rep. 2020;21(4): e48467.PubMedPubMedCentral
76.
Ding C, Xi G, Wang G, Cui D, Zhang B, Wang H, et al. Exosomal circ-MEMO1 promotes the progression and aerobic glycolysis of non-small cell lung cancer through targeting MiR-101–3p/KRAS axis. Front Genet. 2020;11:962.PubMedPubMedCentral
77.
Wang S, Zhan J, Lin X, Wang Y, Wang Y, Liu Y. CircRNA-0077930 from hyperglycaemia-stimulated vascular endothelial cell exosomes regulates senescence in vascular smooth muscle cells. Cell Biochem Funct. 2020;38(8):1056–68.PubMed
78.
79.
Xu W, Deng B, Lin P, Liu C, Li B, Huang Q, et al. Ribosome profiling analysis identified a KRAS-interacting microprotein that represses oncogenic signaling in hepatocellular carcinoma cells. Sci China Life Sci. 2020;63(4):529–42.PubMed
Metadata
Title
Emerging role of non-coding RNAs in the regulation of KRAS
Authors
Soudeh Ghafouri-Fard
Zeinab Shirvani-Farsani
Bashdar Mahmud Hussen
Mohammad Taheri
Reza Jalili Khoshnoud
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02486-1

Other articles of this Issue 1/2022

Cancer Cell International 1/2022 Go to the issue

Research

Lymphocyte antigen 6G6D-mediated modulation through p38α MAPK and DNA methylation in colorectal cancer

Primary research

High AKAP8L expression predicts poor prognosis in esophageal squamous cell carcinoma

Primary research

CARM1 promotes gastric cancer progression by regulating TFE3 mediated autophagy enhancement through the cytoplasmic AMPK-mTOR and nuclear AMPK-CARM1-TFE3 signaling pathways

Primary research

Quantification of fibrinogen-to-pre-albumin ratio provides an integrating parameter for differential diagnosis and risk stratification of early-stage colorectal cancer

Retraction Note

Retraction Note to: Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells

Review

Periostin: biology and function in cancer
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