Abstract
The outcomes of patients with SCLC have not yet been substantially impacted by the revolution in precision oncology, primarily owing to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. Although, these results are encouraging, many patients do not respond to, or rapidly recur after, current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion, is a snapshot of the current biomarker and clinical trial landscapes for SCLC. Finally, we identify key knowledge gaps that should be addressed to advance the field in pursuit of reduced SCLC mortality. This review largely summarizes work presented at the Third Biennial International Association for the Study of Lung Cancer SCLC Meeting.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 520-540 |
| Number of pages | 21 |
| Journal | Journal of Thoracic Oncology |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2020 |
Keywords
- ASCL1
- Gene mutations
- Neuroendocrine
- SCLC
- Therapy
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
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New Approaches to SCLC Therapy : From the Laboratory to the Clinic. / Poirier, John T.; George, Julie; Owonikoko, Taofeek K. et al.
In: Journal of Thoracic Oncology, Vol. 15, No. 4, 04.2020, p. 520-540.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - New Approaches to SCLC Therapy
T2 - From the Laboratory to the Clinic
AU - Poirier, John T.
AU - George, Julie
AU - Owonikoko, Taofeek K.
AU - Berns, Anton
AU - Brambilla, Elisabeth
AU - Byers, Lauren A.
AU - Carbone, David
AU - Chen, Huanhuan J.
AU - Christensen, Camilla L.
AU - Dive, Caroline
AU - Farago, Anna F.
AU - Govindan, Ramaswamy
AU - Hann, Christine
AU - Hellmann, Matthew D.
AU - Horn, Leora
AU - Johnson, Jane E.
AU - Ju, Young S.
AU - Kang, Sumin
AU - Krasnow, Mark
AU - Lee, James
AU - Lee, Se Hoon
AU - Lehman, Jonathan
AU - Lok, Benjamin
AU - Lovly, Christine
AU - MacPherson, David
AU - McFadden, David
AU - Minna, John
AU - Oser, Matthew
AU - Park, Keunchil
AU - Park, Kwon Sik
AU - Pommier, Yves
AU - Quaranta, Vito
AU - Ready, Neal
AU - Sage, Julien
AU - Scagliotti, Giorgio
AU - Sos, Martin L.
AU - Sutherland, Kate D.
AU - Travis, William D.
AU - Vakoc, Christopher R.
AU - Wait, Sarah J.
AU - Wistuba, Ignacio
AU - Wong, Kwok Kin
AU - Zhang, Hua
AU - Daigneault, Jillian
AU - Wiens, Jacinta
AU - Rudin, Charles M.
AU - Oliver, Trudy G.
N1 - Funding Information: The authors were supported by grants from the National Institutes of Health (NIH) R01 CA213448 (Dr. Poirier and Dr. Rudin), U01 CA213359 (Dr. Poirier), U01 CA231844 (Dr. Oliver and Dr. Govindan), U24 CA213274 (Dr. Rudin and Dr. Oliver), U01 CA213338 (Dr. Minna), R21 CA216504 (Dr. Oliver), and R01 CA207295 (Dr. Byers). The NCI Small Cell Research Consortium Coordinating Center ( U24 CA213274 ) and the International Association for the Study of Lung Cancer supported the meeting on which this review is based. The authors also thank Dr. Peter Ujhazy, Dr. Eva Szabo, and Dr. Suzanne Forry from the National Cancer Institute (NCI), and Dr. Adi Gazdar, whose pioneering work has greatly impacted the discoveries described in this study, and to whom the Third Biennial International Association for the Study of Lung Cancer (IASLC) SCLC meeting and this manuscript was dedicated to. Funding Information: Disclosure: Dr. Owonikoko reports personal fees from G1 Therapeutics outside of the submitted work. Dr. Poirier has a patent pending for DLL3-targeting antibodies. Dr. Byers reports receiving personal fees from AstraZeneca, AbbVie, GenMab, BergenBio, Pharma Mar, Sierra Oncology, Bristol-Myers Squibb (BMS), Alethia Biotherapeutics Inc., and Merck and Co. outside of the submitted work. Dr. Carbone reports personal fees from AbbVie, Adaptimmune, Agenus, Amgen, Ariad, AstraZeneca, Boehringer Ingelheim, EMD Serono, Inc., Foundation Medicine, Genentech/Roche, Gritstone, Guardant Health, Helsinn, Incyte, Inivata, Inovio, Janssen, Kyowa Kirin, Loxo Oncology, Merck, MSD, Nexus Oncology, Novartis, Palobiofarma, Pfizer, prIME Oncology, Stemcentrx, and Takeda Oncology, and grants and personal fees from BMS outside of the submitted work. Dr. Dive reports receiving grants from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, GlaxoSmithKline (GSK), Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Epigene Therapeutics Inc, Angle plc, Menarini, and Clearbridge Biomedics outside of the submitted work; he also received honoraria from Biocartis, AstraZeneca, Cold Springs Harbor Laboratory, and Karolinska Institutet for consulting work and lectures, and as a reviewer outside of the submitted work. Dr. Farago reports receiving grants and personal fees from AbbVie, AstraZeneca, BMS, Loxo Bayer, PharmaMar, Genentech, and Roche; personal fees from Boehringer Ingelheim; and grants from Amgen, Merck, and Ignyta outside of the submitted work. Dr. Govindan reports receiving personal fees from INC Research, AbbVie, Eli Lilly, Inivata, Pfizer, AstraZeneca, Genentech-Roche, Millennium Pharmaceuticals, F. Hoffman La-Roche, NeoHealth, Janssen, BMS, Nektar, Merck Celgene Phillips Gilmore, GSK, Jounce, Amgen, and Achilles over the past 36 months outside of the submitted work. Dr. Hann reports receiving grants and personal fees from AbbVie, BMS, Ascentage and Genentech/Roche during the conduct of the study; she also received grants from Merrimack outside of the submitted work. Dr. Hellmann reports receiving personal fees from Merck, Genentech/Roche, Mirati, Syndax, Shattuck Laboratories, Nektar, and Immunai; grants, personal fees, and nonfinancial support from BMS; and personal fees and nonfinancial support from AstraZeneca during the conduct of the study. In addition, Dr. Hellmann has a patent filed by Memorial Sloan Kettering related to the use of tumor mutational burden to predict response to immunotherapy (PCT/US2015/062208) licensed to PGDx. Dr. Horn reports receiving personal fees from AstraZeneca, AbbVie, Incyte, EMD Serono, Merck, Pfizer, Roche-Genentech, and Tessaro; grants and personal fees from BMS and Xcovery; and grants from Boehringer Ingelheim outside of the submitted work. Dr. Se-Hoon Lee reports receiving grants from MSD and personal fees from Novartis, AstraZeneca, BMS, Ono, and Roche outside of the submitted work. Dr. Lehman reports receiving nonfinancial support from AbbVie/StemCentrx during the conduct of the study and grants from Ipsen outside of the submitted work. Dr. Lok reports consulting fees from Pfizer outside of the submitted work. Dr. Lovly reports grants from National Institutes of Health (NIH)/National Cancer Institute (NCI), the Lung Cancer Foundation of America, and the International Association for the Study of Lung Cancer (IASLC) during the conduct of the study and consulting fees from Takeda, BluePrints Medicine, Foundation Medicine, Achilles, Pfizer, Ariad, Novartis, AstraZeneca, Cepheid, and Roche outside of the submitted work. Dr. MacPherson reports receiving grants from Roche during the conduct of the study and grants from Janssen outside of the submitted work. Dr. Minna reports receiving grants from the NCI during the conduct of the study and personal fees from NCI and University of Texas Southwestern Medical Center outside of the submitted work. Dr. Oser has a structured research agreement from AstraZeneca for future projects related to this work and received personal fees from HVH Precision Analytics outside of the submitted work. Dr. Keunchil Park reports receiving grants from AstraZeneca during the conduct of the study; consulting fees from Astellas, AstraZeneca, Amgen, BluePrint, Boehringer Ingelheim, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Merck KGaA, Ono, and Roche; and grants and other from MSD outside of the submitted work. Dr. Ready reports receiving grants and personal fees from BMS and Merck; and personal fees from Celgene, G1 Therapeutics, AstraZeneca, Novartis, AbbVie, EMD Serono, Pfizer, and Genentech outside of the submitted work. Dr. Sage reports receiving grants from Revolution Medicine, Pfizer, and AbbVie/StemCentrx outside of the submitted work. In addition, Dr. Sage has a patent PCT/US2015/010650 licensed to Forty-Seven, Inc. Dr. Scagliotti reports receiving personal fees from Eli Lilly, Roche, AbbVie, MSD, AstraZeneca, Regeneron, and Takeda outside of the submitted work. Dr. Sos reports receiving grants from Novartis and consulting fees from PearlRiver Bio outside of the submitted work. In addition, Dr. Sos has patent methods and compositions pending for identifying and treating patients with SCLC. Dr. Sutherland reports grants from the National Health and Medical Research Council (NHMRC; APP1159955), holds a Peter and Julie Alston WEHI Centenary Fellowship, and has received an anonymous donation for SCLC research. Dr. Sutherland also reports receiving direct research support from Agios Pharmaceuticals and Pfizer Pharmaceuticals; honoraria from Agios Pharmaceuticals; and grants from NHMRC (APP1138275) and a Victorian Cancer Agency Mid-Career Fellowship (MCRF18003) outside of the submitted work. Dr. Vakoc is an advisor to KSQ Therapeutics and has received research funding from Boehringer Ingelheim outside of the submitted work. Dr. Wistuba reports receiving grants and personal fees from Genentech/Roche, BMS, Bayer, AstraZeneca/Medimmune, Pfizer, Merck, HTG Molecular, Asuragen, and Guardant; personal fees from Boehringer Ingelheim, Ariad and GlaxoSmithKline; and grants from DepArray, Oncoplex, Adaptive, Adaptimmune, EMD Serono, Takeda, Amgen, Novartis, Immatics, and Karus outside of the submitted work. Dr. Wong reports receiving grants from NCI outside of the submitted work. Dr. Rudin reports receiving grants from NIH/NCI during the conduct of the study and personal fees from AbbVie, Amgen, Ascentage, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Genentech/Roche, Ipsen, Loxo, Pharmamar, and Harpoon outside of the submitted work. Dr. Oliver reports receiving grants from NCI and the Lung Cancer Research Foundation, honorarium from Pfizer, and preclinical compounds from Polaris Pharmaceuticals during the conduct of the study. In addition, Dr. Oliver has patents pending in the United States, Europe, and Japan patent offices. The remaining authors declare no conflict of interest.The authors were supported by grants from the National Institutes of Health (NIH) R01 CA213448 (Dr. Poirier and Dr. Rudin), U01 CA213359 (Dr. Poirier), U01 CA231844 (Dr. Oliver and Dr. Govindan), U24 CA213274 (Dr. Rudin and Dr. Oliver), U01 CA213338 (Dr. Minna), R21 CA216504 (Dr. Oliver), and R01 CA207295 (Dr. Byers). The NCI Small Cell Research Consortium Coordinating Center (U24 CA213274) and the International Association for the Study of Lung Cancer supported the meeting on which this review is based. The authors also thank Dr. Peter Ujhazy, Dr. Eva Szabo, and Dr. Suzanne Forry from the National Cancer Institute (NCI), and Dr. Adi Gazdar, whose pioneering work has greatly impacted the discoveries described in this study, and to whom the Third Biennial International Association for the Study of Lung Cancer (IASLC) SCLC meeting and this manuscript was dedicated to. Publisher Copyright: © 2020 International Association for the Study of Lung Cancer
PY - 2020/4
Y1 - 2020/4
N2 - The outcomes of patients with SCLC have not yet been substantially impacted by the revolution in precision oncology, primarily owing to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. Although, these results are encouraging, many patients do not respond to, or rapidly recur after, current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion, is a snapshot of the current biomarker and clinical trial landscapes for SCLC. Finally, we identify key knowledge gaps that should be addressed to advance the field in pursuit of reduced SCLC mortality. This review largely summarizes work presented at the Third Biennial International Association for the Study of Lung Cancer SCLC Meeting.
AB - The outcomes of patients with SCLC have not yet been substantially impacted by the revolution in precision oncology, primarily owing to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. Although, these results are encouraging, many patients do not respond to, or rapidly recur after, current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion, is a snapshot of the current biomarker and clinical trial landscapes for SCLC. Finally, we identify key knowledge gaps that should be addressed to advance the field in pursuit of reduced SCLC mortality. This review largely summarizes work presented at the Third Biennial International Association for the Study of Lung Cancer SCLC Meeting.
KW - ASCL1
KW - Gene mutations
KW - Neuroendocrine
KW - SCLC
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=85080093069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85080093069&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2020.01.016
DO - 10.1016/j.jtho.2020.01.016
M3 - Review article
C2 - 32018053
AN - SCOPUS:85080093069
VL - 15
SP - 520
EP - 540
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 4
ER -