Chemical Reviews pubs.acs.
org/CR Review
(364) Pulciani, S.; Santos, E.; Lauver, A. V.; Long, L. K.; Aaronson, (382) Ostrem, J. M.; Peters, U.; Sos, M. L.; Wells, J. A.; Shokat, K.
S. A.; Barbacid, M. Oncogenes in Solid Human Tumours. Nature M. K-Ras(G12C) Inhibitors Allosterically Control GTP Affinity and
1982, 300, 539−542. Effector Interactions. Nature 2013, 503, 548−551.
(365) Vaishnavi, A.; Le, A. T.; Doebele, R. C. TRKing Down an Old (383) Canon, J.; Rex, K.; Saiki, A. Y.; Mohr, C.; Cooke, K.; Bagal,
Oncogene in a New Era of Targeted Therapy. Cancer Discovery 2015, D.; Gaida, K.; Holt, T.; Knutson, C. G.; Koppada, N.; et al. The
5, 25−34. Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour
(366) Doebele, R. C.; Davis, L. E.; Vaishnavi, A.; Le, A. T.; Estrada- Immunity. Nature 2019, 575, 217−223.
Bernal, A.; Keysar, S.; Jimeno, A.; Varella-Garcia, M.; Aisner, D. L.; Li, (384) Christensen, J. G.; Hallin, J.; Engstrom, L. D.; Hargis, L.;
Y.; et al. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Calinisan, A.; Aranda, R.; Briere, D. M.; Sudhakar, N.; Bowcut, V.;
Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor Baer, B. R.; et al. The KRASG12C Inhibitor, MRTX849, Provides
LOXO-101. Cancer Discovery 2015, 5, 1049−1057. Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers
(367) Huang, F. W.; Feng, F. Y. A Tumor-Agnostic NTRK (TRK) in Mouse Models and Patients. Cancer Discovery 2020, 10, 54−71.
(385) Race For Undruggable KRAS Speeds Up. Nat. Biotechnol.
Inhibitor. Cell 2019, 177, 8.
2019, 37, 1247..
(368) Drilon, A.; Siena, S.; Ou, S.-H. I.; Patel, M.; Ahn, M. J.; Lee, J.;
(386) Vasan, N.; Baselga, J.; Hyman, D. M. A View on Drug
Bauer, T. M.; Farago, A. F.; Wheler, J. J.; Liu, S. V.; et al. Safety and
Resistance in Cancer. Nature 2019, 575, 299−309.
Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK
Inhibitor Entrectinib: Combined Results from Two Phase I Trials
(ALKA-372−001 and STARTRK-1). Cancer Discovery 2017, 7, 400−
409.
(369) Cocco, E.; Scaltriti, M.; Drilon, A. NTRK fusion-positive
cancers and TRK inhibitor therapy. Nat. Rev. Clin. Oncol. 2018, 15,
731−747.
(370) Blake, J.; Kolakowski, G. R.; Tuch, B.; Ebata, K.; Brandhuber,
B.; Winski, S.; Bouhana, K.; Nanda, N.; Wu, W. I.; Parker, A.; et al.
The Development of LOXO-195, a Second Generation TRK Kinase
Inhibitor that Overcomes Acquired Resistance to 1st Generation
Inhibitors Observed in Patients with TRK-Fusion Cancers. Eur. J.
Cancer 2016, 69, S144−S145.
(371) Rodon Ahnert, J.; Gray, N.; Mok, T.; Gainor. What It Takes
to Improve a First-Generation Inhibitor to a Second- or Third-
Generation Small Molecule. J. Am. Soc. Clin. Oncol. Educ. Book. 2019,
39, 196−205.
(372) Laurini, E.; Posocco, P.; Fermeglia, M.; Gibbons, D. L.;
Quintas-Cardama, A.; Pricl, S. Through the Open Door: Preferential
Binding of Dasatinib to the Active Form of BCR-ABL Unveiled by In
Silico Experiments. Mol. Oncol. 2013, 7, 968−975.
(373) Deshaies, R. J. Prime time for PROTACs. Nat. Chem. Biol.
2015, 11, 634−635.
(374) Zhang, L.; Riley-Gillis, B.; Vijay, P.; Shen, Y. Acquired
Resistance to BET-PROTACs (Proteolysis-Targeting Chimeras)
Caused by Genomic Alterations in Core Components of E3 Ligase
Complexes. Mol. Cancer Ther. 2019, 18, 1302−1311.
(375) Jacus, M. O.; Daryani, V. M.; Harstead, K. E.; Patel, Y. T.;
Throm, S. L.; Stewart, C. F. Pharmacokinetic Properties of Anticancer
Agents for the Treatment of Central Nervous System Tumors:
Update of the Literature. Clin. Pharmacokinet. 2016, 55, 297−311.
(376) Yang, Z.; Guo, Q.; Wang, Y.; Chen, K.; Zhang, L.; Cheng, Z.;
Xu, Y.; Yin, X.; Bai, Y.; Rabbie, S.; Kim, D. W.; Ahn, M. J.; Yang, J. C.;
Zhang, X. AZD3759, a BBB-Penetrating EGFR Inhibitor for the
Treatment of EGFR Mutant NSCLC with CNS Metastases. Sci.
Transl. Med. 2016, 8, 368ra172.
(377) Ballard, P.; Yates, J. W.; Yang, Z.; Kim, D. W.; Yang, J. C.;
Cantarini, M.; Pickup, K.; Jordan, A.; Hickey, M.; Grist, M.; et al.
Preclinical Comparison of Osimertinib with Other EGFR-TKIs in
EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence
of Clinical Brain Metastases Activity. Clin. Cancer Res. 2016, 22,
5130−5140.
(378) Coombes, R. Cancer Drug Resistance Needs Urgent
Attention, Says Research Chief. BMJ. 2019, 365, l1934.
(379) Day, D.; Siu, L. L. Approaches to Modernize the Combination
Drug Development Paradigm. Genome Med. 2016, 8, 115.
(380) Celebi, R.; Bear Don’t Walk, O., IV; Movva, R.; Alpsoy, S.;
Dumontier, M. In-Silico Prediction of Synergistic Anti-Cancer Drug
Combinations Using Multi-omics Data. Sci. Rep. 2019, 9, 8949.
(381) Pylayeva-Gupta, Y.; Grabocka, E.; Bar-Sagi, D. RAS
oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer 2011, 11,
761−774.
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