Clinical complexity of utilizing FGFR inhibitors in cancer therapeutics

References

• Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet. 2004;20:563–569.
   PubMed Web of Science ®Google Scholar
• Turner N, Grose R. Fibroblast growth factor signalling from development to cancer. Nat Rev Cancer. 2010;10:116–129.
   PubMed Web of Science ®Google Scholar
• Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer. 2017;17:318–332.
   PubMed Web of Science ®Google Scholar
• Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2016 Jan 1;22(1):259–267.
   PubMed Web of Science ®Google Scholar
• Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology.Nat. Rev Clin Oncol. 2019 Feb;16(2):105–122.
   PubMed Web of Science ®Google Scholar
• The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discov. 2017;7(8):818–831. Dataset Version 4.
   PubMed Web of Science ®Google Scholar
• Touat M, Ileana E, Postel-Vinay S, et al. Targeting FGFR Signaling in Cancer. Clin Cancer Res. 2015 June 15;21(12):2684–2694.
   PubMed Web of Science ®Google Scholar
• Squires M, Ward G, Saxty G, et al. Potent, selective inhibitors of fibroblast growth factor receptor define fibroblast growth factor dependence in preclinical cancer models. Mol Cancer Ther. 2011 Sept;10(9):1542–1552.
   PubMed Web of Science ®Google Scholar
• Perera TPS, Jovcheva E, Mevellec L, et al. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther. 2017 June;16(6):1010–1020.
   PubMed Web of Science ®Google Scholar
• Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015 Oct 20;33(30):3401–3408.
   PubMed Web of Science ®Google Scholar
• Collin MP, Lobell M, Hübsch W, et al. Discovery of Rogaratinib (BAY 1163877): a pan‐FGFR inhibitor. ChemMedChem. 2018;13:1–10.
   Web of Science ®Google Scholar
• Grünewald S, Politz O, Bender S, et al. Rogaratinib: a potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019;145:1346–1357.
   PubMed Web of Science ®Google Scholar
• Schuler M, Cho BC, Sayehli CM, et al. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Oct;20(10):1454–1466.
   PubMed Web of Science ®Google Scholar
• Kalyukina M, Yosaatmadja Y, Middleditch MJ, et al. TAS-120 cancer target binding: defining reactivity and revealing the first fibroblast growth factor receptor 1 (FGFR1) irreversible structure. ChemMedChem. 2019 Feb 19;14(4):494–500.
   PubMed Web of Science ®Google Scholar
• Futami T, Okada H, Kihara R, et al. ASP5878, a novel inhibitor of FGFR1, 2, 3, and 4, inhibits the growth of FGF19-expressing hepatocellular carcinoma. Mol Cancer Ther. 2017;16(1):68–75.
   PubMed Web of Science ®Google Scholar
• Yamamoto N, Ryoo B, Keam B, et al. A phase 1 study of oral ASP5878, a selective small-molecule inhibitor of fibroblast growth factor receptors 1–4, as a single dose and multiple doses in patients with solid malignancies. Invest New Drugs. 2020;38:445–456.
   PubMed Web of Science ®Google Scholar
• Sequist LV, Cassier P, Varga A, et al. Abstract CT326: phase I study of BGJ398, a selective pan-FGFR inhibitor in genetically preselected advanced solid tumors. Cancer Res. 2014;74(19):CT326–CT326.
   Google Scholar
• Liu PC, Wu L, Koblish H, et al. Preclinical characterization of the selective FGFR inhibitor INCB054828. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18–22; Philadelphia (PA): AACR; Cancer Res 2015; 75(15Suppl):Abstract nr 771.
   Google Scholar
• Subbiah V, Barve M, Iannotti N, et al. A phase 1/2 study of pemigatinib, a highly selective fibroblast growth factor receptor (FGFR) inhibitor, as monotherapy and as combination therapy in patients with advanced malignancies. Mol Cancer Ther. 2019 Dec 1;18(12 Supplement):A078.
   Web of Science ®Google Scholar
• Voss MH, Hierro C, Heist RS, et al. A phase i, open-label, multicenter, dose-escalation study of the oral selective FGFR inhibitor debio 1347 in patients with advanced solid tumors harboring FGFR gene alterations. Clin Cancer Res. 2019 May 1;25(9):2699–2707.
   PubMed Web of Science ®Google Scholar
• Hall TG, Yu Y, Eathiraj S, et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS One. 2016 Sept 14;11(9):e0162594.
   PubMed Web of Science ®Google Scholar
• Papadopoulos K, El-Rayes B, Tolcher A, et al. A phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours. Br J Cancer. 2017;117:1592–1599.
   PubMed Web of Science ®Google Scholar
• Kim RD, Sarker D, Meyer T, et al. First-in-human phase I study of fisogatinib (BLU-554) validates aberrant FGF19 signaling as a driver event in hepatocellular carcinoma. Cancer Discov. 2019 Dec;9(12):1696–1707.
   PubMed Web of Science ®Google Scholar
• Hatlen MA, Schmidt-Kittler O, Sherwin CA, et al. Acquired on-target clinical resistance validates FGFR4 as a driver of hepatocellular carcinoma. Cancer Discov. 2019;9(12):1686–1695.
   PubMed Web of Science ®Google Scholar
• French DM, Lin BC, Wang M, et al. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models. PLoS One. 2012;7:e36713.
   PubMed Web of Science ®Google Scholar
• Joshi JJ, Coffey H, Corcoran E, et al. H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-driven hepatocellular carcinoma. Cancer Res. 2017 Dec 15;77(24):6999–7013.
   PubMed Web of Science ®Google Scholar
• Mercade TM, Moreno V, Binu J, et al. A phase I study of H3B-6527 in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) patients. J clin oncol. 2019;37(15_suppl):4095.
   Web of Science ®Google Scholar
• Weiss A, Adler F, Buhles A, et al. FGF401, a first-in-class highly selective and potent FGFR4 inhibitor for the treatment of FGF19-driven hepatocellular cancer. Mol Cancer Ther. 2019 Aug 13;18:2194–2206.
   Web of Science ®Google Scholar
• Gemo AT, Deshpande AM, Palencia S, et al. FPA144: a therapeutic antibody for treating patients with gastric cancers bearing FGFR2 gene amplification. Cancer Res. 2014;74:abstr 5446.
   Web of Science ®Google Scholar
• Catenacci DVT, Rasco D, Lee J, et al. Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma. J Clin Oncol. 2020 Mar 13;JCO1901834.
   Google Scholar
• Catenacci DVT, Tesfaye A, Tejani M, et al. Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design. Future Oncol. 2019;15:2073–2082.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, Picus J, Kohli M, et al. FIERCE-21: phase Ib/II study of docetaxel + b-701, a selective inhibitor of FGFR3, in relapsed or refractory (R/R) metastatic urothelial carcinoma (mUCC). J Clin Oncol. 2018;36(15 Suppl.):4534.
   Google Scholar
• Necchi A, Castellano DE, Mellado B, et al. Fierce-21: phase II study of vofatmab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC). J Clin Oncol. 2019;37(7 Suppl.):409.
   Google Scholar
• Kamath AV, Lu D, Gupta P, et al. Preclinical pharmacokinetics of MFGR1877A, a human monoclonal antibody to FGFR3, and prediction of its efficacious clinical dose for the treatment of t(4;14)-positive multiple myeloma. Cancer Chemother Pharmacol. 2012 Apr;69(4):1071–1078.
   PubMed Web of Science ®Google Scholar
• Odonnell P, Goldman JW, Gordon MS, et al. A phase I dose-escalation study of MFGR1877S, a human monoclonal anti-fibroblast growth factor receptor 3 (FGFR3) antibody, in patients (pts) with advanced solid tumors. Eur J Cancer. 2012;48:191–192.
   Web of Science ®Google Scholar
• Trudel S, Bergsagel PL, Singhal S, et al. A phase I study of the safety and pharmacokinetics of escalating doses of MFGR1877S, a fibroblast growth factor receptor 3 (FGFR3) antibody, in patients with relapsed or refractory t(4;14)-positive multiple myeloma. ASH Ann Meet Abstr. 2012;120:4029.
   Google Scholar
• Bartz R, Fukuchi K, Ohtsuka T, et al. Preclinical development of U3-1784, a novel FGFR4 antibody against cancer, and avoidance of its on-target toxicity. Mol Cancer Ther. 2019 Oct 1;18(10):1832–1843.
   PubMed Web of Science ®Google Scholar
• Sommer A, Kopitz C, Schatz CA, et al. Preclinical efficacy of the auristatin-based antibody-drug conjugate BAY 1187982 for the treatment of FGFR2-positive solid tumors. Cancer Res. 2016 Nov 1;76(21):6331–6339.
   PubMed Web of Science ®Google Scholar
• Kim SB, Meric-Bernstam F, Kalyan A, et al. First-in-human phase i study of aprutumab ixadotin, a fibroblast growth factor receptor 2 antibody-drug conjugate (BAY 1187982) in patients with advanced cancer. Target Oncol. 2019 Oct;14(5):591–601.
   PubMed Web of Science ®Google Scholar
• Surguladze D, Pennello A, Ren X, et al. LY3076226, a novel anti-FGFR3 antibody drug conjugate exhibits potent and durable anti-tumor activity in tumor models harboring FGFR3 mutations or fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019; 79(13Suppl):Abstract nr 4835.
   Google Scholar
• Maier KE, Levy M. From selection hits to clinical leads: progress in aptamer discovery. Mol Ther Methods Clin Dev. 2016;5:16014.
   PubMed Web of Science ®Google Scholar
• Stoltenburg R, Reinemann C, Strehlitz B. SELEX–a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng. 2007;24:381–403.
   PubMedGoogle Scholar
• Jin L, Nonaka Y, Miyakawa S, et al. Dual therapeutic action of a neutralizing anti-FGF2 aptamer in bone disease and bone cancer pain. Mol Ther. 2016;24:1974–1986.
   PubMed Web of Science ®Google Scholar
• Hamamoto J, Yasuda H, Nonaka Y, et al. The FGF2 aptamer inhibits the growth of FGF2-FGFR pathway driven lung cancer cells. Biochem Biophys Res Commun. 2018 Sept 10;503(3):1330–1334.
   PubMed Web of Science ®Google Scholar
• Terai H, Soejima K, Yasuda HS, et al. Activation of the FGF2-FGFR1 autocrine pathway: a novel mechanism of acquired resistance to gefitinib in NSCLC. Mol Cancer Res. 2013;11:759–767.
   PubMed Web of Science ®Google Scholar
• Kamatkar N, Levy M, Hébert JM. Development of a monomeric Inhibitory RNA aptamer specific for FGFR3 that acts as an activator when dimerized. Mol Ther Nucleic Acids. 2019 Sept 6;17:530–539.
   PubMedGoogle Scholar
• Jurek PM, Zabłocki K, Waśko U, et al. Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy. Int J Nanomedicine. 2017 Apr 11;12:2941–2950.
   PubMed Web of Science ®Google Scholar
• Billerey C, Chopin D, Aubriot-Lorton MH, et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol. 2001 June;158(6):1955–1959.
   PubMed Web of Science ®Google Scholar
• Loriot Y, Necchi A, Park SH, et al. Erdafitinib in Locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019 July 25;381(4):338–348.
   PubMed Web of Science ®Google Scholar
• Moreno V, Loriot Y, Valderrama BP, et al. Dose escalation results from phase Ib/II Norse study of erdafitinib (ERDA) + PD-1 inhibitor JNJ-63723283 (Cetrelimab [CET]) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) gene alterations. J clin oncol. 2020;38(6_suppl):511.
   Web of Science ®Google Scholar
• Pal SK, Rosenberg JE, Hoffman-Censits JH, et al. Efficacy of BGJ398, a fibroblast growth factor receptor 1-3 Inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations. Cancer Discov. 2018 July;8(7):812–821.
   PubMed Web of Science ®Google Scholar
• Pal SK, Bajorin D, Dizman N, et al. Infigratinib in upper tract urothelial carcinoma versus urothelial carcinoma of the bladder and its association with comprehensive genomic profiling and/or cell-free DNA results. Cancer. 2020;126:2597–2606.
   Web of Science ®Google Scholar
• Necchi A, Pouessel D, Leibowitz-Amit R, et al. Interim results of Fight-201, a phase 2, open-label, multicenter study of INCB054828 dosed intermittently in patients with metastatic or surgically unresectable urothelial carcinoma (UC) harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations (GA). Ann Oncol. 2018;29:viii303–31.
   Web of Science ®Google Scholar
• Siefker-Radtke AO, Currie G, Abella E, et al. FIERCE-22: clinical activity of vofatamab (V) a FGFR3 selective inhibitor in combination with pembrolizumab (P) in WT metastatic urothelial carcinoma, preliminary analysis. J clin oncol. 2019;37(15_suppl):4511.
   Web of Science ®Google Scholar
• Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014 Apr;59(4):1427–1434.
   PubMed Web of Science ®Google Scholar
• Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next‐generation sequencing. Oncologist. 2014;19:235–242.
   PubMed Web of Science ®Google Scholar
• Sia D, Losic B, Cabellos L, et al. Discovery of novel mutations and fusion proteins in intrahepatic cholangiocarcinoma. J Hepatol. 2014;60:S41. [abstract O‐019].
   Web of Science ®Google Scholar
• Xu YF, Yang XQ, Lu XF, et al. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma. Biochem Biophys Res Commun. 2014;446:54–60.
   PubMed Web of Science ®Google Scholar
• Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45:1630–1638.
   PubMed Web of Science ®Google Scholar
• Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018 Sept 1;24(17):4154–4161.
   PubMed Web of Science ®Google Scholar
• Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36(3):276–282.
   PubMed Web of Science ®Google Scholar
• Park JO, Feng Y, Chen Y, et al. Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations. J clin oncol. 2019;37(15_suppl):4117.
   Web of Science ®Google Scholar
• Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicenter, open-label, phase 2 study. Lancet Oncol. 2020 May;21(5):671–684.
   PubMed Web of Science ®Google Scholar
• Mazzaferro V, El-Rayes BF, Droz Dit Busset M, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120:165–171.
   PubMed Web of Science ®Google Scholar
• Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion–positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019 Aug 1;9(8):1064–1079.
   PubMed Web of Science ®Google Scholar
• Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010;2:62ra93.
   PubMed Web of Science ®Google Scholar
• Paik PK, Shen R, Berger MF, et al. A phase Ib open-label multicenter study of AZD4547 in patients with advanced squamous cell lung cancers. Clin Cancer Res. 2017 Sept 15;23(18):5366–5373.
   PubMed Web of Science ®Google Scholar
• Aggarwal C, Redman MW, Lara PN, et al. SWOG S1400D (NCT02965378), a phase II study of the fibroblast growth factor receptor inhibitor AZD4547 in previously-treated patients with fibroblast growth factor pathway-activated stage IV squamous cell lung cancer (Lung-MAP Sub-Study). J Thorac Oncol. 2019;14:1847–1852.
   PubMed Web of Science ®Google Scholar
• Joerger M, Cho BC, Mach N, et al. Early clinical experience with the pan-FGFR inhibitor rogaratinib in patients with non-small cell lung cancer selected based on FGFR mRNA expression levels. J Clin Oncol. 2019;37(suppl; abstr e20661):15s.
   Google Scholar
• Bass A, Thorsson V, Shmulevich I, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209.
   PubMed Web of Science ®Google Scholar
• Su X, Zhan P, Gavine PR, et al. FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study. Br J Cancer. 2014;110:967–975.
   PubMed Web of Science ®Google Scholar
• Kunii K, Davis L, Gorenstein J, et al. FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008;68:2340–2348.
   PubMed Web of Science ®Google Scholar
• Xie L, Su X, Zhang L, et al. FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547. Clin Cancer Res. 2013;19:2572–2583.
   PubMed Web of Science ®Google Scholar
• Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21:449–456.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Bang YJ, Mansoor W, et al. A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification. Ann Oncol. 2017 June 1;28(6):1316–1324.
   PubMed Web of Science ®Google Scholar
• Chao J, Bedell V, Lee J, et al. Association between spatial heterogeneity within nonmetastatic gastroesophageal adenocarcinomas and survival. JAMA Network Open. 2020 Apr 1;3(4):e203652.
   PubMed Web of Science ®Google Scholar
• Konecny GE, Finkler N, Garcia AA, et al. Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study. Lancet Oncol. 2015;16:686–694.
   PubMed Web of Science ®Google Scholar
• Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337:1231–1235.
   PubMed Web of Science ®Google Scholar
• Chae YK, Vaklavas C, Cheng HH, et al. Molecular analysis for therapy choice (MATCH) arm W: phase II study of AZD4547 in patients with tumors with aberrations in the FGFR pathway. Proc Am Soc Clin Oncol. 2018;36(suppl 15):2503.
   Google Scholar
• Joerger M, Takahashi S, Sayehli CM, et al. Phase I experience with rogaratinib in patients with head and neck cancer selected based on FGFR mRNA overexpression. Ann Oncol. 2018;29:viii372–99.
   Google Scholar
• Qiu H, Yashiro M, Zhang X, et al. A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells. Cancer Lett. 2011;307(1):47–52.
   PubMed Web of Science ®Google Scholar
• Yashiro M, Shinto O, Nakamura K, et al. Synergistic antitumor effects of FGFR2 inhibitor with 5-fluorouracil on scirrhous gastric carcinoma. Int J Cancer. 2010;126(4):1004–1016.
   PubMed Web of Science ®Google Scholar
• Musolino A, Campone M, Neven P, et al. Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2− breast cancer that had progressed during or after prior endocrine therapy. Breast Cancer Res. 2017 Feb 10;19(1):18.
   PubMedGoogle Scholar
• Takamura T, Horinaka M, Yasuda S, et al. FGFR inhibitor BGJ398 and HDAC inhibitor OBP-801 synergistically inhibit cell growth and induce apoptosis in bladder cancer cells. Oncol Rep. 2018;39:627–632.
   PubMed Web of Science ®Google Scholar
• Krook MA, Lenyo L, Wilberding M, et al. Efficacy of FGFR inhibitors and combination therapies for acquired resistance in FGFR2-fusion cholangiocarcinoma. Mol Cancer Ther. 2020 Jan 7;19:847–857.
   PubMed Web of Science ®Google Scholar
• Palakurthi S, Kuraguchi M, Zacharek SJ, et al. The combined effect of FGFR inhibition and PD-1 blockade promotes tumor-intrinsic induction of antitumor immunity. Cancer Immunol Res. 2019 Sept 1;7(9):1457–1471.
   PubMed Web of Science ®Google Scholar
• Yin Y, Zuo W, Yan H, et al. Genomic landscape of FGF/FGFR pathway alternations across 12,372 pan-cancer patients. JCO. 2020;38(15_suppl):e13503.
   Web of Science ®Google Scholar
• Pon JR, Marra MA. Driver and passenger mutations in cancer. Annu Rev Pathol. 2015;10:25–50.
   PubMed Web of Science ®Google Scholar
• Chakraborty S, Hosen MI, Ahmed M, et al. Onco-multi-OMICS approach: a new frontier in cancer research. Biomed Res Int. 2018;2018:9836256.
   PubMed Web of Science ®Google Scholar
• Phan N, Hong JJ, Tofig B, et al. A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids. Commun Biol. 2019;2:78.
   PubMed Web of Science ®Google Scholar
• Herrera-Abreu MT, Pearson A, Campbell J, et al. Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer. Cancer Discov. 2013 Sept;3(9):1058–1071.
   PubMed Web of Science ®Google Scholar
• Hu Y, Lu H, Zhang J, et al. Essential role of AKT in tumor cells addicted to FGFR. Anticancer Drugs. 2014;25(2):183–188.
   PubMed Web of Science ®Google Scholar
• Yoza K, Himeno R, Amano S, et al. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1. Genes Cells. 2016;21:1049–1058.
   PubMed Web of Science ®Google Scholar
• Chell V, Balmanno K, Little AS, et al. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene. 2013 June 20;32(25):3059–3070.
   PubMed Web of Science ®Google Scholar
• Kas SM, de Ruiter J, Schut E, et al. Transcriptomics and transposon mutagenesis identify multiple mechanisms of resistance to the FGFR inhibitor AZD4547. Cancer Res. 2018;78:5668–5679.
   PubMed Web of Science ®Google Scholar
• Goyal L, Saha SK, Liu LY, et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov. 2017;7:252–263.
   PubMed Web of Science ®Google Scholar
• Yanochko GM, Vitsky A, Heyen JR, et al. Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction. Toxicol Sci. 2013;135:451–464.
   PubMed Web of Science ®Google Scholar
• Velazquez-Villoria D, Azaro A, Rodon J, et al. Novel ocular toxicity associated with fibroblast growth factor receptor (FGFR) inhibitors in cancer treatment: observational case series. Br J Ophthalmol. 103:bjophthalmol–2017.
   Google Scholar
• Betrian S, Gomez-Roca C, Vigarios E, et al. Severe onycholysis and eyelash trichomegaly following use of new selective pan-FGFR inhibitors. JAMA Dermatol. 2017;153:723–725.
   PubMed Web of Science ®Google Scholar
• Chow-White P, Ha D, Laskin J. Knowledge, attitudes, and values among physicians working with clinical genomics: a survey of medical oncologists. Hum Resour Health. 2017;15(1):42.
   PubMedGoogle Scholar
• Koil CE, Everett JN, Hoechstetter L, et al. Differences in physician referral practices and attitudes regarding hereditary breast cancer by clinical practicenlocation. Genet Med. 2003;5(5):364–369.
   PubMed Web of Science ®Google Scholar
• Larson K, Kannaiyan R, Pandey R, et al. A comparative analysis of tumors and plasma circulating tumor DNA in 145 advanced cancer patients annotated by 3 core cellular processes. Cancers (Basel). 2020 Mar 16;12(3):701.
   Web of Science ®Google Scholar
• Kuderer NM, Burton KA, Blau S, et al. Comparison of 2 commercially available next-generation sequencing platforms in oncology. JAMA Oncol. 2017 July 1;3(7):996–998.
   PubMed Web of Science ®Google Scholar
• Santiago-Walker AE, Moy C, Cherkas Y, et al. Analysis of FGFR alterations from circulating tumor DNA (ctDNA) and Tissue in a phase II trial of erdafitinib in urothelial carcinoma (UC). J clin oncol. 2019;37(7_suppl):420.
   Web of Science ®Google Scholar
• Ekwueme DU, Yabroff KR, Guy GP, et al. Medical costs and productivity losses of cancer survivors–United States, 2008–2011. MMWR Morb Mortal Wkly Rep. 2014;63(23):505–510.
   PubMed Web of Science ®Google Scholar
• Guy GP, Yabroff KR, Ekwueme DU, et al. Estimating the health and economic burden of cancer among those diagnosed as adolescents and young adults. Health Aff (Millwood). 2014;33(6):1024–1031.
   PubMed Web of Science ®Google Scholar
• Bradley CJ, Yabroff KR, Warren JL, et al. Trends in the treatment of metastatic colon and rectal cancer in elderly patients. Med Care. 2016;54(5):490–497.
   PubMed Web of Science ®Google Scholar
• Shih YC, Smieliauskas F, Geynisman DM, et al. Trends in the cost and use of targeted cancer therapies for the privately insured nonelderly: 2001 to 2011. J Clin Oncol. 2015;33(19):2190–2196.
   PubMed Web of Science ®Google Scholar
• Young RC. Value-based cancer care. N Engl J Med. 2015;373:2593–2595.
   PubMed Web of Science ®Google Scholar
• Chino F, Peppercorn JM, Rushing C, et al. Out-of-pocket costs, financial distress, and underinsurance in cancer care. JAMA Oncol. 2017;3:1582.
   PubMed Web of Science ®Google Scholar
• Inokuchi M, Murase H, Otsuki S, et al. Different clinical significance of FGFR1-4 expression between diffuse-type and intestinal-type gastric cancer. World J Surg Oncol. 2017;15(1):2.
   PubMedGoogle Scholar