Prospects of focal adhesion kinase inhibitors as a cancer therapy in preclinical and early phase study

References

• Schaller MD, Borgman CA, Cobb BS, et al. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–6. doi: 10.1073/pnas.89.11.5192
   PubMed Web of Science ®Google Scholar
• Tapial Martínez P, López Navajas P, Lietha D. FAK structure and regulation by membrane interactions and force in focal adhesions. Biomolecules. 2020 Jan 24;10(2):179.
   PubMed Web of Science ®Google Scholar
• Hildebrand JD, Schaller MD, Parsons JT. Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. J Cell Bio. 1993 Nov;123(4):993–1005. doi: 10.1083/jcb.123.4.993
   PubMed Web of Science ®Google Scholar
• Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci. 2003 Apr 15;116(Pt 8):1409–1416.
   PubMed Web of Science ®Google Scholar
• Spallarossa A, Tasso B, Russo E, et al. The development of FAK inhibitors: a five-year update. Int J Mol Sci. 2022 Jun 7;23(12):6381. doi: 10.3390/ijms23126381
   PubMed Web of Science ®Google Scholar
• Le Coq J, Acebrón I, Rodrigo Martin B, et al. New insights into FAK structure and function in focal adhesions. J Cell Sci. 2022 Oct 15;135(20). doi: 10.1242/jcs.259089
   PubMed Web of Science ®Google Scholar
• Wörthmüller J, Rüegg C. The crosstalk between FAK and wnt signaling pathways in cancer and its therapeutic implication. Int J Mol Sci. 2020 Nov 30;21(23):9107.
   PubMed Web of Science ®Google Scholar
• Li S, Hua ZC. FAK expression regulation and therapeutic potential. Adv Cancer Res. 2008;101:1–454. doi: 10.1016/S0065-230X(08)00403-X
   PubMed Web of Science ®Google Scholar
• Lechertier T, Hodivala-Dilke K. Focal adhesion kinase and tumour angiogenesis. J Pathol. 2012 Jan;226(2):404–412. doi: 10.1002/path.3018
   PubMed Web of Science ®Google Scholar
• Lee BY, Timpson P, Horvath LG, et al. FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 2015 Feb;146:132–149. doi: 10.1016/j.pharmthera.2014.10.001
   PubMed Web of Science ®Google Scholar
• Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nat Rev Cancer. 2014 Sep;14(9):598–610. doi: 10.1038/nrc3792
   PubMed Web of Science ®Google Scholar
• Schaller MD. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010 Apr 1;123(Pt 7):1007–1013.
   PubMed Web of Science ®Google Scholar
• Golubovskaya VM, Kweh FA, Cance WG. Focal adhesion kinase and cancer. Histol Histopathol. 2009 Apr;24(4):503–510. doi: 10.14670/HH-24.503
   PubMed Web of Science ®Google Scholar
• Park JH, Lee BL, Yoon J, et al. Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer. Hum Pathol. 2010 Dec;41:(12):1664–1673.
   PubMed Web of Science ®Google Scholar
• Luo M, Guan JL. Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis. Cancer Lett. 2010 Mar 28;289(2):127–139.
   PubMed Web of Science ®Google Scholar
• Ozmadenci D, Shankara Narayanan JS, Andrew J, et al. Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis. Proc Natl Acad Sci USA. 2022 Apr 26;119(17):e2117065119. doi: 10.1073/pnas.2117065119
   PubMed Web of Science ®Google Scholar
• Paradis JS, Acosta M, Saddawi-Konefka R, et al. Synthetic lethal screens reveal cotargeting FAK and MEK as a multimodal precision therapy for GNAQ-Driven Uveal Melanoma. Clin Cancer Res. 2021 Jun 1;27(11):3190–3200. doi: 10.1158/1078-0432.CCR-20-3363
   PubMed Web of Science ®Google Scholar
• Murphy JM, Rodriguez YAR, Jeong K, et al. Targeting focal adhesion kinase in cancer cells and the tumor microenvironment. Exp Mol Med. 2020 Jun;52:(6):877–886.
   PubMed Web of Science ®Google Scholar
• Uchihara T, Miyake K, Yonemura A, et al. Extracellular vesicles from cancer-associated fibroblasts containing annexin A6 induces FAK-YAP activation by stabilizing β1 integrin, enhancing drug resistance. Cancer Res. 2020 Aug 15;80(16):3222–3235. doi: 10.1158/0008-5472.CAN-19-3803
   PubMed Web of Science ®Google Scholar
• Lander VE, Belle JI, Kingston NL, et al. Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade. Cancer Discov. 2022 Dec 2;12(12):2774–2799. doi: 10.1158/2159-8290.CD-22-0192
   PubMed Web of Science ®Google Scholar
• Roy-Luzarraga M, Abdel-Fatah T, Reynolds LE, et al. Association of low tumor endothelial cell pY397-focal adhesion kinase expression with survival in patients with neoadjuvant-treated locally advanced breast cancer. JAMA Netw Open. 2020 Oct 1;3(10):e2019304. doi: 10.1001/jamanetworkopen.2020.19304
   PubMed Web of Science ®Google Scholar
• Lim Y, Lim ST, Tomar A, et al. PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility. J Cell Bio. 2008 Jan 14;180(1):187–203. doi: 10.1083/jcb.200708194
   PubMed Web of Science ®Google Scholar
• Li H, Peyrollier K, Kilic G, et al. Rho GTPases and cancer. BioFactors. 2014 Mar;40:(2):226–235.
   PubMed Web of Science ®Google Scholar
• Zhai J, Lin H, Nie Z, et al. Direct interaction of focal adhesion kinase with p190RhoGEF. J Biol Chem. 2003 Jul 4;278(27):24865–24873. doi: 10.1074/jbc.M302381200
   PubMed Web of Science ®Google Scholar
• Brábek J, Constancio SS, Shin NY, et al. CAS promotes invasiveness of src-transformed cells. Oncogene. 2004 Sep 23;23(44):7406–7415. doi: 10.1038/sj.onc.1207965
   PubMed Web of Science ®Google Scholar
• Cary LA, Han DC, Polte TR, et al. Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration. J Cell Bio. 1998 Jan 12;140(1):211–221. doi: 10.1083/jcb.140.1.211
   PubMed Web of Science ®Google Scholar
• Sharma A, Mayer BJ. Phosphorylation of p130Cas initiates Rac activation and membrane ruffling. BMC Cell Biol. 2008 Sep 15;9(1):50.
   PubMedGoogle Scholar
• Cao Q, Mao ZD, Shi YJ, et al. MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway. Oncotarget. 2016 Nov 22;7(47):77468–77481. doi: 10.18632/oncotarget.12684
   PubMedGoogle Scholar
• Zhang J, He DH, Zajac-Kaye M, et al. A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143–3149. doi: 10.4161/15384101.2014.949550
   PubMed Web of Science ®Google Scholar
• Li B, Li Y, Tomkiewicz-Raulet C, et al. Design, synthesis, and biological evaluation of covalent inhibitors of focal adhesion kinase (FAK) against human malignant glioblastoma. J Med Chem. 2020 Nov 12;63(21):12707–12724. doi: 10.1021/acs.jmedchem.0c01059
   PubMed Web of Science ®Google Scholar
• Timbrell S, Aglan H, Cramer A, et al. FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity. NPJ Breast Cancer. 2021 May 28;7(1):65. doi: 10.1038/s41523-021-00263-3
   PubMed Web of Science ®Google Scholar
• Qin J, Tang J, Jiao L, et al. A diterpenoid compound, excisanin A, inhibits the invasive behavior of breast cancer cells by modulating the integrin β1/FAK/PI3K/AKT/β-catenin signaling. Life Sci. 2013 Nov 4;93(18–19):655–663. doi: 10.1016/j.lfs.2013.09.002
   PubMed Web of Science ®Google Scholar
• Shang N, Arteaga M, Zaidi A, et al. FAK is required for c-Met/β-catenin-driven hepatocarcinogenesis. Hepatology. 2015 Jan;61:(1):214–226.
   PubMed Web of Science ®Google Scholar
• Kolev VN, Tam WF, Wright QG, et al. Inhibition of FAK kinase activity preferentially targets cancer stem cells. Oncotarget. 2017 Aug 1;8(31):51733–51747. doi: 10.18632/oncotarget.18517
   PubMedGoogle Scholar
• Zhao Z, Zhang Y, Guo E, et al. Periostin secreted from podoplanin-positive cancer-associated fibroblasts promotes metastasis of gastric cancer by regulating cancer stem cells via AKT and YAP signaling pathway. Mol Carcinog. 2023 May;62:(5):685–699.
   PubMed Web of Science ®Google Scholar
• Lin L, Sabnis AJ, Chan E, et al. The hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat Genet. 2015 Mar;47:(3):250–256.
   PubMed Web of Science ®Google Scholar
• Dey A, Varelas X, Guan KL. Targeting the hippo pathway in cancer, fibrosis, wound healing and regenerative medicine. Nat Rev Drug Discov. 2020 Jul;19(7):480–494. doi: 10.1038/s41573-020-0070-z
   PubMed Web of Science ®Google Scholar
• Zanconato F, Cordenonsi M, Piccolo S. YAP/TAZ at the roots of cancer. Cancer Cell. 2016 Jun 13;29(6):783–803.
   PubMed Web of Science ®Google Scholar
• Lachowski D, Cortes E, Robinson B, et al. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis. Faseb J. 2018 Feb;32:(2):1099–1107.
   PubMed Web of Science ®Google Scholar
• Nguyen CDK, Yi C. YAP/TAZ signaling and resistance to cancer therapy. Trends Cancer. 2019 May;5(5):283–296. doi: 10.1016/j.trecan.2019.02.010
   PubMed Web of Science ®Google Scholar
• Fisher ML, Grun D, Adhikary G, et al. Inhibition of YAP function overcomes BRAF inhibitor resistance in melanoma cancer stem cells. Oncotarget. 2017 Dec 15;8(66):110257–110272. doi: 10.18632/oncotarget.22628
   PubMedGoogle Scholar
• Zhang B, Zhang Y, Zhang J, et al. Focal adhesion kinase (FAK) inhibition synergizes with KRAS G12C inhibitors in treating cancer through the regulation of the FAK-YAP signaling. Adv Sci (Weinh). 2021 Aug;8(16):e2100250. doi: 10.1002/advs.202100250
   PubMedGoogle Scholar
• Gao J, Yao Y, Liu C, et al. Synergism of FAK and ROS1 inhibitors in the treatment of CDH1-deficient cancers mediated by FAK-YAP signaling. Int J Biol Sci. 2023;19(9):2711–2724. doi: 10.7150/ijbs.81918
   PubMed Web of Science ®Google Scholar
• Das T, Anand U, Pandey SK, et al. Therapeutic strategies to overcome taxane resistance in cancer. Drug Resist Updat. 2021 Mar;55:100754. doi: 10.1016/j.drup.2021.100754
   PubMed Web of Science ®Google Scholar
• Amawi H, Sim HM, Tiwari AK, et al. ABC Transporter-Mediated Multidrug-Resistant Cancer. Adv Exp Med Biol. 2019;1141:549–580.
   PubMed Web of Science ®Google Scholar
• Fan J, To KKW, Chen ZS, et al. ABC transporters affects tumor immune microenvironment to regulate cancer immunotherapy and multidrug resistance. Drug Resist Updat. 2023 Jan;66:100905. doi: 10.1016/j.drup.2022.100905
   PubMed Web of Science ®Google Scholar
• Ji N, Yang Y, Cai CY, et al. VS-4718 antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells by inhibiting the efflux function of ABC transporters. Front Pharmacol. 2018;9:1236. doi: 10.3389/fphar.2018.01236
   PubMed Web of Science ®Google Scholar
• Canel M, Serrels A, Miller D, et al. Quantitative in vivo imaging of the effects of inhibiting integrin signaling via src and FAK on cancer cell movement: effects on E-cadherin dynamics. Cancer Res. 2010 Nov 15;70(22):9413–9422. doi: 10.1158/0008-5472.CAN-10-1454
   PubMed Web of Science ®Google Scholar
• Ma RR, Zhang H, Chen HF, et al. MiR-19a/miR-96-mediated low expression of KIF26A suppresses metastasis by regulating FAK pathway in gastric cancer. Oncogene. 2021 Apr;40:(14):2524–2538.
   PubMed Web of Science ®Google Scholar
• Peiró S, Escriva, M, Puig, I, et al. Snail1 transcriptional repressor binds to its own promoter and controls its expression. Nucleic Acids Res. 2006;34(7):2077–2084. doi: 10.1093/nar/gkl141
   PubMed Web of Science ®Google Scholar
• Ganesan R, Mallets E, Gomez-Cambronero J. The transcription factors slug (SNAI2) and snail (SNAI1) regulate phospholipase D (PLD) promoter in opposite ways towards cancer cell invasion. Mol Oncol. 2016 May;10(5):663–676. doi: 10.1016/j.molonc.2015.12.006
   PubMed Web of Science ®Google Scholar
• Yang J, Hou Y, Zhou M, et al. Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network. Int J Biochem Cell Biol. 2016 Feb;71:62–71. doi: 10.1016/j.biocel.2015.12.004
   PubMed Web of Science ®Google Scholar
• Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020 Aug 17;30(16):R921–r925.
   PubMed Web of Science ®Google Scholar
• Jin MZ, Jin WL. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther. 2020 Aug 25;5(1):166.
   PubMed Web of Science ®Google Scholar
• Xing F. Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front Biosci (Landmark Ed). 2010 Jan 1;15(1):166–179.
   PubMedGoogle Scholar
• Papait A, Romoli J, Stefani FR, et al. Fight the cancer, hit the CAF! Cancers (Basel). 2022 Jul 22;14(15):3570. doi: 10.3390/cancers14153570
   PubMed Web of Science ®Google Scholar
• Demircioglu F, Wang J, Candido J, et al. Cancer associated fibroblast FAK regulates malignant cell metabolism. Nat Commun. 2020 Mar 10;11(1):1290. doi: 10.1038/s41467-020-15104-3
   PubMed Web of Science ®Google Scholar
• Sexton RE, Al Hallak MN, Diab M, et al. Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer Metastasis Rev. 2020 Dec;39:(4):1179–1203.
   PubMed Web of Science ®Google Scholar
• Roy-Luzarraga M, Hodivala-Dilke K. Molecular pathways: endothelial cell FAK-A target for cancer treatment. Clin Cancer Res. 2016 Aug 1;22(15):3718–3724.
   PubMed Web of Science ®Google Scholar
• Wu HJ, Hao M, Yeo SK, et al. FAK signaling in cancer-associated fibroblasts promotes breast cancer cell migration and metastasis by exosomal miRnas-mediated intercellular communication. Oncogene. 2020 Mar;39:(12):2539–2549.
   PubMed Web of Science ®Google Scholar
• Lim ST. Nuclear FAK: a new mode of gene regulation from cellular adhesions. Mol Cells. 2013 Jul;36(1):1–6. doi: 10.1007/s10059-013-0139-1
   PubMed Web of Science ®Google Scholar
• Borst J, Ahrends T, Bąbała N, et al. CD4(+) T cell help in cancer immunology and immunotherapy. Nat Rev Immunol. 2018 Oct;18:(10):635–647.
   PubMed Web of Science ®Google Scholar
• Serrels A, Lund T, Serrels B, et al. Nuclear FAK controls chemokine transcription, tregs, and evasion of anti-tumor immunity. Cell. 2015 Sep 24;163(1):160–173. doi: 10.1016/j.cell.2015.09.001
   PubMed Web of Science ®Google Scholar
• Serrels B, McGivern N, Canel M, et al. IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through transcriptional networks. Sci Signal. 2017 Dec 5;10(508). doi: 10.1126/scisignal.aan8355
   PubMed Web of Science ®Google Scholar
• Dawson JC, Serrels A, Stupack DG, et al. Targeting FAK in anticancer combination therapies. Nat Rev Cancer. 2021 May;21:(5):313–324.
   PubMed Web of Science ®Google Scholar
• Davidson C, Taggart D, Sims AH, et al. FAK promotes stromal PD-L2 expression associated with poor survival in pancreatic cancer. Br J Cancer. 2022 Nov;127:(10):1893–1905.
   PubMed Web of Science ®Google Scholar
• Canel M, Sławińska AD, Lonergan DW, et al. FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer. Gut. 2023 Mar 28;73(1):131–155. doi: 10.1136/gutjnl-2022-327927
   PubMed Web of Science ®Google Scholar
• Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016 Aug;22:(8):851–860.
   PubMed Web of Science ®Google Scholar
• Braren R, Hu H, Kim YH, et al. Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation. J Cell Bio. 2006 Jan 2;172(1):151–162. doi: 10.1083/jcb.200506184
   PubMed Web of Science ®Google Scholar
• Pedrosa AR, Bodrug N, Gomez-Escudero J, et al. Tumor angiogenesis is differentially regulated by phosphorylation of endothelial cell focal adhesion kinase tyrosines-397 and -861. Cancer Res. 2019 Sep 1;79(17):4371–4386. doi: 10.1158/0008-5472.CAN-18-3934
   PubMed Web of Science ®Google Scholar
• Sun S, Wu HJ, Guan JL. Nuclear FAK and its kinase activity regulate VEGFR2 transcription in angiogenesis of adult mice. Sci Rep. 2018 Feb 7;8(1):2550.
   PubMedGoogle Scholar
• Lee J, Borboa AK, Chun HB, et al. Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma. Cancer Res. 2010 Dec 15;70(24):10131–10140. doi: 10.1158/0008-5472.CAN-10-2740
   PubMed Web of Science ®Google Scholar
• Chen XL, Nam JO, Jean C, et al. VEGF-induced vascular permeability is mediated by FAK. Dev Cell. 2012 Jan 17;22(1):146–157. doi: 10.1016/j.devcel.2011.11.002
   PubMed Web of Science ®Google Scholar
• Jean C, Chen XL, Nam JO, et al. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function. J Cell Bio. 2014 Jan 20;204(2):247–263. doi: 10.1083/jcb.201307067
   PubMed Web of Science ®Google Scholar
• Brullo C, Tasso B. New insights on fak and fak inhibitors. Curr Med Chem. 2021;28(17):3318–3338. doi: 10.2174/0929867327666201103162239
   PubMed Web of Science ®Google Scholar
• Pang X-J, Liu X-J, Liu Y, et al. Drug discovery targeting focal adhesion kinase (FAK) as a promising cancer therapy. Molecules. 2021;26(14):4250. doi: 10.3390/molecules26144250
   PubMed Web of Science ®Google Scholar
• Lu Y, Sun H. Progress in the development of small molecular inhibitors of focal adhesion kinase (FAK). J Med Chem. 2020 Dec 10;63(23):14382–14403.
   PubMed Web of Science ®Google Scholar
• Stahl E, Nott R, Koessel K, et al. Computational-based discovery of FAK FERM domain chemical probes that inhibit HER2-FAK cancer signaling. Chem Biol Drug Des. 2020 Jun;95:(6):584–599.
   PubMed Web of Science ®Google Scholar
• Golubovskaya VM, Nyberg C, Zheng M, et al. A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth. J Med Chem. 2008 Dec 11;51(23):7405–7416. doi: 10.1021/jm800483v
   PubMed Web of Science ®Google Scholar
• Gerber DE, Camidge DR, Morgensztern D, et al. Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer. Lung Cancer. 2020 Jan;139:60–67. doi: 10.1016/j.lungcan.2019.10.033
   PubMed Web of Science ®Google Scholar
• Patel MR, Infante JR, Moore KN, et al. Phase 1/1b study of the FAK inhibitor defactinib (VS-6063) in combination with weekly paclitaxel for advanced ovarian cancer. J Clin Oncol. 2014;32(15_suppl):5521–5521. doi: 10.1200/jco.2014.32.15_suppl.5521
   Web of Science ®Google Scholar
• Vidal CM, Kolev VN, Wright QG, et al. Abstract C271: FAK inhibitor defactinib (VS-6063) enhances the efficacy of paclitaxel and preferentially targets ovarian cancer stem cells. Mol Cancer Ther. 2013;12(11_Supplement):C271–C271. doi: 10.1158/1535-7163.TARG-13-C271
   Web of Science ®Google Scholar
• Richardson DL, Eskander RN, O’Malley DM. Advances in ovarian cancer care and unmet treatment needs for patients with platinum resistance: a narrative review. JAMA Oncol. 2023 Jun 1;9(6):851–859. doi: 10.1001/jamaoncol.2023.0197
   PubMed Web of Science ®Google Scholar
• Martinez-Garcia M, Banerji U, Albanell J, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012;18(17):4806–4819. doi: 10.1158/1078-0432.CCR-12-0742
   PubMed Web of Science ®Google Scholar
• Banerjee SR, Niewenhuysen EV, Fabbro M, et al. #523 initial efficacy and safety results from ENGOT-Ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). Int J Gynecologic Cancer. 2023;33(Suppl 3):A20–A21.
   Google Scholar
• Hirt UA, Braunger J, Schleicher M, et al. Abstract A249: BI 853520, a potent and highly selective inhibitor of protein tyrosine kinase 2 (focal adhesion kinase), shows efficacy in multiple xenograft models of human cancer. Mol Cancer Ther. 2011;10(Supplement 1):A249–A249. doi: 10.1158/1535-7163.TARG-11-A249
   Google Scholar
• Diaz Osterman CJ, Ozmadenci D, Kleinschmidt EG, et al. FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy. Elife. 2019;8:e47327. doi: 10.7554/eLife.47327
   PubMed Web of Science ®Google Scholar
• Vergote I, Wang, Schilder J, et al. A phase Ib study of IN10018 in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2022;40(16_suppl):5567–5567. doi: 10.1200/JCO.2022.40.16_suppl.5567
   Web of Science ®Google Scholar
• Soria JC, Gan HK, Blagden SP, et al. A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors. Ann Oncol. 2016 Dec;27:(12):2268–2274.
   PubMed Web of Science ®Google Scholar
• Murphy JM, Jeong K, Lim SS. FAK family kinases in vascular diseases. IJMS. 2020 May 21;21(10):3630.
   Google Scholar
• Walsh C, Tanjoni I, Uryu S, et al. Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther. 2010 May 15;9(10):778–790. doi: 10.4161/cbt.9.10.11433
   PubMed Web of Science ®Google Scholar
• Kargbo RB. Chemically induced degradation of FAK-ALK for application in cancer therapeutics. ACS Med Chem Lett. 2020 Jul 9;11(7):1367–1368.
   PubMedGoogle Scholar
• Schoenherr C, Byron A, Sandilands E, et al. Ambra1 spatially regulates src activity and Src/FAK-mediated cancer cell invasion via trafficking networks. Elife. 2017 Mar 31;6. doi: 10.7554/eLife.23172
   PubMed Web of Science ®Google Scholar
• Chuang HH, Zhen YY, Tsai YC, et al. FAK in cancer: from mechanisms to therapeutic strategies. Int J Mol Sci. 2022 Feb 2;23(3):1726. doi: 10.3390/ijms23031726
   PubMed Web of Science ®Google Scholar
• Serrels B, Serrels A, Brunton VG, et al. Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat Cell Biol. 2007 Sep;9:(9):1046–1056.
   PubMed Web of Science ®Google Scholar
• Luo M, Zhao X, Chen S, et al. Distinct FAK activities determine progenitor and mammary stem cell characteristics. Cancer Res. 2013 Sep 1;73(17):5591–5602. doi: 10.1158/0008-5472.CAN-13-1351
   PubMed Web of Science ®Google Scholar
• Yousefi H, Vatanmakanian M, Mahdiannasser M, et al. Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance. Oncogene. 2021 Feb;40:(6):1043–1063.
   PubMed Web of Science ®Google Scholar
• Hirt UA, Waizenegger IC, Schweifer N, et al. Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype. Oncogenesis. 2018 Feb 23;7(2):21. doi: 10.1038/s41389-018-0032-z
   PubMedGoogle Scholar
• Jones SF, Siu LL, Bendell JC, et al. A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015 Oct;33:(5):1100–1107.
   PubMed Web of Science ®Google Scholar
• Shimizu T, Fukuoka K, Takeda M, et al. A first-in-asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 May;77:(5):997–1003.
   PubMed Web of Science ®Google Scholar
• Liu F, Tong D, Li H, et al. Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway. Oncotarget. 2016 Feb 23;7(8):8896–8907. doi: 10.18632/oncotarget.6840
   PubMedGoogle Scholar
• Lin HM, Lee BY, Castillo L, et al. Effect of FAK inhibitor VS-6063 (defactinib) on docetaxel efficacy in prostate cancer. Prostate. 2018 Mar;78:(4):308–317.
   PubMed Web of Science ®Google Scholar
• Halder J, Landen CN Jr., Lutgendorf SK, et al. Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells. Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8829–8836. doi: 10.1158/1078-0432.CCR-05-1728
   PubMed Web of Science ®Google Scholar
• Li XY, Shi LX, Yao XM, et al. Functional vinorelbine plus schisandrin B liposomes destroying tumor metastasis in treatment of gastric cancer. Drug Dev Ind Pharm. 2021 Jan;47:(1):100–112.
   PubMed Web of Science ®Google Scholar
• Symeonides SN, Anderton SM, Serrels A. FAK-inhibition opens the door to checkpoint immunotherapy in pancreatic cancer. J Immunother Cancer. 2017;5(1):17. doi: 10.1186/s40425-017-0217-6
   PubMedGoogle Scholar
• Wei Y, Wang Y, Liu N, et al. A FAK inhibitor boosts anti-PD1 immunotherapy in a hepatocellular carcinoma mouse model. Front Pharmacol. 2021;12:820446. doi: 10.3389/fphar.2021.820446
   PubMed Web of Science ®Google Scholar
• Wu L, Wang J, Wang L, et al. 753P IN10018 in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (PROC): a single-arm, phase Ib clinical trial. Ann Oncol. 2023 Oct 01;34:S516.
   Web of Science ®Google Scholar