Unravelling the biology of SCLC: Implications for therapy Journal Article
| Authors: | Sabari, J. K.; Lok, B. H.; Laird, J. H.; Poirier, J. T.; Rudin, C. M. |
| Article Title: | Unravelling the biology of SCLC: Implications for therapy |
| Abstract: | Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints.Preclinical data indicate that targeting of histone-lysine N-methyltransferase EZH2, a regulator of chromatin remodelling implicated in acquired therapeutic resistance, might augment and prolong chemotherapy responses. High expression of the inhibitory Notch ligand Delta-like protein 3 (DLL3) in most SCLCs has been linked to expression of Achaete-scute homologue 1 (ASCL1; also known as ASH-1), a key transcription factor driving SCLC oncogenesis; encouraging preclinical and clinical activity has been demonstrated for an anti-DLL3-antibody-drug conjugate. The immune microenvironment of SCLC seems to be distinct from that of other solid tumours, with few tumour-infiltrating lymphocytes and low levels of the immune-checkpoint protein programmed cell death 1 ligand 1 (PD-L1). Nonetheless, immunotherapy with immune-checkpoint inhibitors holds promise for patients with this disease, independent of PD-L1 status. Herein, we review the progress made in uncovering aspects of the biology of SCLC and its microenvironment that are defining new therapeutic strategies and offering renewed hope for patients. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| Journal Title: | Nature Reviews Clinical Oncology |
| Volume: | 14 |
| Issue: | 9 |
| ISSN: | 1759-4774 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-09-01 |
| Start Page: | 549 |
| End Page: | 561 |
| Language: | English |
| DOI: | 10.1038/nrclinonc.2017.71 |
| PROVIDER: | scopus |
| PUBMED: | 28534531 |
| PMCID: | PMC5843484 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 5 September 2017 -- Source: Scopus |
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