Villanueva, A. Hepatocellular carcinoma. N. Engl. J. Med. 380, 1450–1462 (2019).
Kudo, M. et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391, 1163–1173 (2018).
Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).
Zucman-Rossi, J., Villanueva, A., Nault, J.-C. & Llovet, J. M. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149, 1226–1239 (2015).
Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).
Finn, R. S. et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 382, 1894–1905 (2020).
Evers, B. et al. CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes. Nat. Biotechnol. 34, 631–633 (2016).
Zhu, A. X. et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J. Clin. Oncol. 33, 559–566 (2015).
Matsuki, M. et al. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 7, 2641–2653 (2018).
Wagle, M.-C. et al. A transcriptional MAPK Pathway Activity Score (MPAS) is a clinically relevant biomarker in multiple cancer types. NPJ Precis. Oncol. 2, 7 (2018).
Pirker, R. et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 13, 33–42 (2012).
Kimura, T. et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model. Cancer Sci. 109, 3993–4002 (2018).
Li, E., Lin, L., Chen, C. W. & Ou, D. L. Mouse models for immunotherapy in hepatocellular carcinoma. Cancers (Basel) 11, 1800 (2019).
Keng, V. W. et al. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat. Biotechnol. 27, 264–274 (2009).
He, H. et al. Platelet-derived growth factor requires epidermal growth factor receptor to activate p21-activated kinase family kinases. J. Biol. Chem. 276, 26741–26744 (2001).
Lee, S.-W. et al. EGFR–Pak signaling selectively regulates glutamine deprivation-induced macropinocytosis. Dev. Cell 50, 381–392 (2019).
Vaseva, A. V. et al. KRAS suppression-induced degradation of MYC is antagonized by a MEK5–ERK5 compensatory mechanism. Cancer Cell 34, 807–822 (2018).
Duncan, J. S. et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 149, 307–321 (2012).
Lito, P. et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 22, 668–682 (2012).
Kosoff, R. E. et al. Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization. Blood 125, 2995–3005 (2015).
Kobayashi, S. et al. Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res. 66, 11389–11398 (2006).
Philip, P. A. et al. Phase II study of erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J. Clin. Oncol. 23, 6657–6663 (2005).
Chan, S. L. et al. New utility of an old marker: serial α-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J. Clin. Oncol. 27, 446–452 (2009).
Llovet, J. M. & Lencioni, R. mRECIST for HCC: performance and novel refinements. J. Hepatol. 72, 288–306 (2020).
Ding, X. et al. Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas. Gastroenterology 157, 1630–1645 (2019).
Cremolini, C. et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann. Oncol. 26, 1188–1194 (2015).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Jin, H. et al. Regulator of calcineurin 1 gene isoform 4, down-regulated in hepatocellular carcinoma, prevents proliferation, migration, and invasive activity of cancer cells and metastasis of orthotopic tumors by inhibiting nuclear translocation of NFAT1. Gastroenterology 153, 799–811 (2017).
Mazières, J. et al. Evaluation of EGFR protein expression by immunohistochemistry using H-score and the magnification rule: re-analysis of the SATURN study. Lung Cancer 82, 231–237 (2013).
Sun, C. et al. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 508, 118–122 (2014).
Wang, L. et al. High-throughput functional genetic and compound screens identify targets for senescence induction in cancer. Cell Rep. 21, 773–783 (2017).
Schuhmacher, M. et al. The transcriptional program of a human B cell line in response to Myc. Nucleic Acids Res. 29, 397–406 (2001).
Wang, C. et al. Inducing and exploiting vulnerabilities for the treatment of liver cancer. Nature 574, 268–272 (2019).
World Medical Association. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull. World Health Organ. 79, 373–374 (2001).