Chemical Reviews pubs.acs.

org/CR Review

(268) Baran, N.; Konopleva, M. Molecular Pathways: Hypoxia- (284) Brennan, C. W.; Verhaak, R. G.; McKenna, A.; Campos, B.;
Activated Prodrugs in Cancer Therapy. Clin. Cancer Res. 2017, 23, Noushmehr, H.; Salama, S. R.; Zheng, S.; Chakravarty, D.; Sanborn, J.
2382−2390. Z.; Berman, S. H.; et al. The Somatic Genomic Landscape of
(269) Koga, T.; Suda, K.; Nishino, M.; Fujino, T.; Ohara, S.; Soh, J.; Glioblastoma. Cell 2013, 155, 462−477.
Vellanki, A.; Tirunagaru, V.; Misudomi, T. Potent in Vitro Activity of (285) Hegi, M. E.; Diserens, A. C.; Bady, P.; Kamoshima, Y.;
Tarloxotinib for HER2 Exon 20 Mutations in Lung Cancer and Kouwenhoven, M. C.; Delorenzi, M.; Lambiv, W. L.; Hamou, M. F.;
Mechanism of Acquired Resistance. J. Thorac. Oncol. 2019, 14, S690. Matter, M. S.; Koch, A.; et al. Pathway Analysis of Glioblastoma
(270) Arcila, M. E.; Nafa, K.; Chaft, J. E.; Rekhtman, N.; Lau, C.; Tissue After Preoperative Treatment with the EGFR Tyrosine Kinase
Reva, B. A.; Zakowski, M. F.; Kris, M. G.; Ladanyi, M. EGFR Exon 20 Inhibitor Gefitinib–A Phase II Trial. Mol. Cancer Ther. 2011, 10,
Insertion Mutations in Lung Adenocarcinomas: Prevalence, Molec- 1102−1112.
ular Heterogeneity, and Clinicopathologic Characteristics. Mol. (286) Sepulveda-Sanchez, J. M.; Vaz, M. A.; Balana, C.; Gil-Gil, M.;
Cancer Ther. 2013, 12, 220−229. Reynes, G.; Gallego, O.; Martinez-Garcia, M.; Vicente, E.; Quindos,
(271) Yasuda, H.; Park, E.; Yun, C. H.; Sng, N. J.; Lucena-Araujo, A. M.; Luque, R.; et al. Phase II Trial of Dacomitinib, a Pan-Human
R.; Yeo, W. L.; Huberman, M. S.; Cohen, D. W.; Nakayama, S.; EGFR Tyrosine Kinase Inhibitor, in Recurrent Glioblastoma Patients
Ishioka, K.; et al. Structural, Biochemical, and Clinical Character- with EGFR Amplification. Neuro. Oncol. 2017, 19, 1522−1531.
ization of Epidermal Growth Factor Receptor (EGFR) Exon 20 (287) Vivanco, I.; Robins, H. I.; Rohle, D.; Campos, C.; Grommes,
Insertion Mutations in Lung Cancer. Sci. Transl. Med. 2013, 5, C.; Nghiemphu, P. L.; Kubek, S.; Oldrini, B.; Chheda, M. G.;
216ra177. Yannuzzi, N.; et al. Differential Sensitivity of Glioma- Versus Lung
(272) Floc’h, N.; Martin, M. J.; Riess, J. W.; Orme, J. P.; Cancer-Specific EGFR Mutations to EGFR Kinase Inhibitors. Cancer
Staniszewska, A. D.; Menard, L.; Cuomo, M. E.; O’Neill, D. J.; Discovery 2012, 2, 458−471.
Ward, R. A.; Finlay, M. R. V.; et al. Antitumor Activity of Osimertinib, (288) O’Connor, M.; Nicolaides, T.; Zhang, J.; Flohr, A.; Iacone, R.;
an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in Mayweg, A. V.; Epstein, D. M.; Buck, E. Epidermal Growth Factor
NSCLC Harboring EGFR Exon 20 Insertions. Mol. Cancer Ther. Receptor Oncogenes Expressed in Glioblastoma are Activated as
2018, 17, 885−896. Covalent Dimers and Exhibit Unique Pharmacology. Cancer Res.
(273) Vyse, S.; Huang, P. H. Targeting EGFR Exon 20 Insertion 2019, 79, LB-111.
Mutations in Non-Small Cell Lung Cancer. Signal Transduct. Target (289) An, K. C. Selective Estrogen Receptor Modulators. Asian Spine
Ther. 2019, 4, 5. J. 2016, 10, 787−791.
(274) Robichaux, J. P.; Elamin, Y. Y.; Tan, Z.; Carter, B. W.; Zhang, (290) Mirkin, S.; Pickar, J. H. Selective Estrogen Receptor
S.; Liu, S.; Li, S.; Chen, T.; Poteete, A.; Estrada-Bernal, A.; et al. Modulators (SERMs): A Review of Clinical Data. Maturitas 2015,
Mechanisms and Clinical Activity of an EGFR and HER2 Exon 20- 80, 52−57.
(291) Dutertre, M.; Smith, C. L. Molecular Mechanisms of Selective
Selective Kinase Inhibitor in Non-Small Cell Lung Cancer. Nat. Med.
Estrogen Receptor Modulator (SERM) Action. J. Pharmacol. Exp.
2018, 24, 638−646.
Ther. 2000, 295, 431−437.
(275) Hasako, S.; Terasaka, M.; Abe, N.; Uno, T.; Ohsawa, H.;
(292) Wakeling, A. E.; Bowler, J. A New Antioestrogen with Clinical
Hashimoto, A.; Fujita, R.; Tanaka, K.; Okayama, T.; Wadhwa, R.;
Potential. J. Steroid Biochem. Mol. Biol. 1992, 43, 173−177.
et al. TAS6417, A Novel EGFR Inhibitor Targeting Exon 20 Insertion
(293) McDonnell, D. P.; Wardell, S. E.; Norris, J. D. Oral Selective
Mutations. Mol. Cancer Ther. 2018, 17, 1648−1658. Estrogen Receptor Downregulators (SERDs), a Breakthrough
(276) Udagawa, H.; Hasako, S.; Ohashi, A.; Fujioka, R.; Hakozaki,
Endocrine Therapy for Breast Cancer. J. Med. Chem. 2015, 58,
Y.; Shibuya, M.; Abe, N.; Komori, T.; Haruma, T.; Terasaka, M.; et al. 4883−4887.
TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine (294) Bentrem, D. J.; Dardes, R. C.; Liu, H.; MacGregor-Schafer, J.;
Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Zapf, J. W.; Jordan, V. C. Molecular Mechanism of Action at Estrogen
Clinically Relevant EGFR Mutations. Mol. Cancer Res. 2019, 17, Receptor α of a New Clinically Relevant Antiestrogen (GW7604)
2233−2243. Related to Tamoxifen. Endocrinology 2001, 142, 838−846.
(277) Doebele, R.; Horn, L.; Spira, A.; Piotrowska, Z.; Costa, D.; (295) Lai, A.; Kahraman, M.; Govek, S.; Nagasawa, J.; Bonnefous,
Neal, J.; Reichmann, W.; Kerstein, D.; Li, S.; Jänne, P. A Phase 1/2 C.; Julien, J.; Douglas, K.; Sensintaffar, J.; Lu, N.; Lee, K.-j.; et al.
Trial of the Oral EGFR/HER2 Inhibitor AP32788 in Non−Small Cell Identification of GDC-0810 (ARN-810), an Orally Bioavailable
Lung Cancer (NSCLC). J. Thorac. Oncol. 2017, 12, S1072−S1073. Selective Estrogen Receptor Degrader (SERD) that Demonstrates
(278) NCT03974022. https://clinicaltrials.gov/ct2/show/ Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts. J.
NCT03974022 (accessed 2020-03). Med. Chem. 2015, 58, 4888−4904.
(279) NCT04209465. https://clinicaltrials.gov/ct2/show/ (296) Nardone, A.; Weir, H.; Delpuech, O.; Brown, H.; De Angelis,
NCT04209465 (accessed 2020-03). C.; Cataldo, M. L.; Fu, X.; Shea, M. J.; Mitchell, T.; Veeraraghavan, J.;
(280) Ward, R. A.; Bianco, A.; Colclough, N.; Cross, D.; Cuomo, E. et al. The Oral Selective Oestrogen Receptor Degrader (SERD)
M.; Finlay, M. R. V.; Fitzek, M.; Floc’h, N.; Gagrica, S.; Hammond, AZD9496 is Comparable to Fulvestrant in Antagonising ER and
B.; et al. Comparative Activity Profiling of Tyrosine Kinase Inhibitors Circumventing Endocrine Resistance. Br. J. Cancer 2019, 120, 331−
(TKIs) Against Exon 20 Insertions and the Wild-Type Form of 339.
Epidermal Growth Factor Receptor (EGFR). Cancer Res. 2019, 79, (297) Bardia, A.; Aftimos, P.; Bihani, T.; Anderson-Villaluz, A. T.;
4813. Jung, J.; Conlan, M. G.; Kaklamani, V. G. Phase III Trial of
(281) Sos, M. L.; Tumbrink, H. L.; Schultz-Fademrecht, C.; Elacestrant (RAD1901) vs Endocrine Therapy for Previously Treated
Lategahn, J.; Keul, M.; Niggenaber, J.; Heimsoeth, A.; Baumann, ER+ Advanced Breast Cancer. Future Oncol. 2019, 15, 3209−3218.
M.; Werr, L. H.; Degenhart, C.; et al. Targeting EGFR Ex20 Mutant (298) Tria, G. S.; Abrams, T.; Baird, J.; Burks, H. E.; Firestone, B.;
Lung Cancer with the Wild Type Sparing Kinase Inhibitor PRB001. J. Gaither, L. A.; Hamann, L. G.; He, G.; Kirby, C. A.; Kim, S.; et al.
Clin. Oncol. 2019, 37, No. e14718. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen
(282) Yoshida, K.; Takeuchi, K.; Inoue, H.; Momose, T.; Yoshida, Receptor Degrader (SERD) for the Treatment of Estrogen Receptor
K.; Jimbo, T.; Egami, A. Biaryl Ether-Type Quinazoline Derivative. Positive Breast Cancer. J. Med. Chem. 2018, 61, 2837−2864.
WO2020009156, 2020. (299) NCT03616587. https://clinicaltrials.gov/ct2/show/
(283) Li, K.; Yang, M.; Liang, N.; Li, S. Determining EGFR-TKI NCT03616587 (accessed 2020-06).
Sensitivity of G719X and Other Uncommon EGFR Mutations in (300) Metcalfe, C.; Ingalla, E.; Blake, R.; Chang, J.; Daemen, A.; De
Non-Small Cell Lung Cancer: Perplexity and Solution (Review). Bruyn, T.; Giltnane, J.; Guan, J.; Hafner, M.; Hartman, S.; et al. GDC-
Oncol. Rep. 2017, 37, 1347−1358. 9545: A Novel ER Antagonist and Clinical Candidate that Combines

AZ https://dx.doi.org/10.1021/acs.chemrev.0c00383
Chem. Rev. XXXX, XXX, XXX−XXX