Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nikanjam M, Liu S, Yang J, Kurzrock R. Dosing three-drug combinations that include targeted anti-cancer agents: analysis of 37,763 patients. Oncologist. 2017;22(5):576–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weiss F, Lauffenburger D, Friedl P. Towards targeting of shared mechanisms of cancer metastasis and therapy resistance. Nat Rev Cancer. 2022;22(3):157–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lund RJ, Huhtinen K, Salmi J, Rantala J, Nguyen EV, Moulder R, et al. DNA methylation and transcriptome changes associated with cisplatin resistance in ovarian cancer. Sci Rep. 2017;7(1):1469.

Article  PubMed  PubMed Central  Google Scholar 

Min HY, Lee HY. Molecular targeted therapy for anticancer treatment. Exp Mol Med. 2022;54(10):1670–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marusyk A, Janiszewska M, Polyak K. Intratumor heterogeneity: the Rosetta Stone of therapy resistance. Cancer Cell. 2020;37(4):471–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu S, Fu L. Tyrosine kinase inhibitors enhanced the efficacy of conventional chemotherapeutic agent in multidrug resistant cancer cells. Mol Cancer. 2018;17(1):25.

Article  PubMed  PubMed Central  Google Scholar 

Bayer. Nexavar : EPAR - Product information https://www.ema.europa.eu/en/medicines/human/EPAR/nexavar#product-info: European Medicines Agency 2009 [updated 18 June 2024.

Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38(5):614–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E. Pharmacokinetics and pharmacogenetics of gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016;78(1):1–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin G, Zhao J, Qi H, Lou M, Liu X, Qu Y, et al. Gemcitabine and carboplatin demonstrate synergistic cytotoxicity in cervical cancer cells by inhibiting DNA synthesis and increasing cell apoptosis. Onco Targets Ther. 2013;6:1707–17.

CAS  PubMed  PubMed Central  Google Scholar 

Carter CA, Chen C, Brink C, Vincent P, Maxuitenko YY, Gilbert KS, et al. Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma. Cancer Chemother Pharmacol. 2007;59(2):183–95.

Article  CAS  PubMed  Google Scholar 

Ricciardi S, Mey V, Nannizzi S, Pasqualetti G, Crea F, Del Tacca M, Danesi R. Synergistic cytotoxicity and molecular interaction on drug targets of sorafenib and gemcitabine in human pancreas cancer cells. Chemotherapy. 2010;56(4):303–12.

Article  CAS  PubMed  Google Scholar 

Pasqualetti G, Ricciardi S, Mey V, Del Tacca M, Danesi R. Synergistic cytotoxicity, inhibition of signal transduction pathways and pharmacogenetics of sorafenib and gemcitabine in human NSCLC cell lines. Lung Cancer. 2011;74(2):197–205.

Article  PubMed  Google Scholar 

Li J, Pan YY, Zhang Y. Sorafenib combined with gemcitabine in EGFR-TKI-resistant human lung cancer cells. Oncol Lett. 2013;5(1):68–72.

Article  CAS  PubMed  Google Scholar 

Jiang S, Wang R, Zhang X, Wu F, Li S, Yuan Y. Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non-small cell lung cancer in vitro and in vivo via the epithelial-to-mesenchymal transition process. Oncol Lett. 2020;20(1):346–56.

PubMed  PubMed Central  Google Scholar 

Takimoto CH, Awada A. Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. Cancer Chemother Pharmacol. 2008;61(4):535–48.

Article  CAS  PubMed  Google Scholar 

Tagawa ST, Milowsky MI, Jeske S, Mazumdar M, Kung S, Sung M, et al. A phase I trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York Cancer Consortium trial NCI 6981. Am J Clin Oncol. 2011;34(5):443–8.

Article  CAS  PubMed  Google Scholar 

Schultheis B, Kummer G, Zeth M, Brendel E, Xia C, Kornacker M, Strumberg D. Phase IB study of sorafenib in combination with gemcitabine and cisplatin in patients with refractory solid tumors. Cancer Chemother Pharmacol. 2012;69(2):333–9.

Article  CAS  PubMed  Google Scholar 

Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, et al. Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2–negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res. 2013;19(10):2745–54.

Article  CAS  PubMed  Google Scholar 

Siu LL, Awada A, Takimoto CH, Piccart M, Schwartz B, Giannaris T, et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res. 2006;12(1):144–51.

Article  CAS  PubMed  Google Scholar 

Aparicio J, García-Mora C, Martín M, Petriz ML, Feliu J, Sánchez-Santos ME, et al. A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. PLoS ONE. 2014;9(1): e82209.

Article  PubMed  PubMed Central  Google Scholar 

Srimuninnimit V, Sriuranpong V, Suwanvecho S. Efficacy and safety of sorafenib in combination with gemcitabine in patients with advanced hepatocellular carcinoma: a multicenter, open-label, single-arm phase II study. Asia Pac J Clin Oncol. 2014;10(3):255–60.

Article  PubMed  Google Scholar 

Liu Y, Yue H, Xu S, Wang F, Ma N, Li K, et al. First-line gemcitabine and oxaliplatin (GEMOX) plus sorafenib, followed by sorafenib as maintenance therapy, for patients with advanced hepatocellular carcinoma: a preliminary study. Int J Clin Oncol. 2015;20(5):952–9.

Article  CAS  PubMed  Google Scholar 

Scagliotti G, Novello S, von Pawel J, Reck M, Pereira JR, Thomas M, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(11):1835–42.

Article  CAS  PubMed  Google Scholar 

Gonçalves A, Gilabert M, François E, Dahan L, Perrier H, Lamy R, et al. BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Ann Oncol. 2012;23(11):2799–805.

Article  PubMed  Google Scholar 

Kindler HL, Wroblewski K, Wallace JA, Hall MJ, Locker G, Nattam S, et al. Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Invest New Drugs. 2012;30(1):382–6.

Article  CAS  PubMed  Google Scholar 

Cascinu S, Berardi R, Sobrero A, Bidoli P, Labianca R, Siena S, et al. Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: a GISCAD randomized phase II study. Dig Liver Dis. 2014;46(2):182–6.

Article  CAS  PubMed  Google Scholar 

Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, et al. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012;30(25):3084–92.

Article