Clinical insights into small cell lung cancer : Tumor heterogeneity, diagnosis, therapy, and future directions
(2023) In CA: a cancer journal for clinicians 73(6). p.620-652- Abstract
Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In... (More)
Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chemotherapy, diagnosis, immunotherapy, molecular subtypes, small cell lung cancer
- in
- CA: a cancer journal for clinicians
- volume
- 73
- issue
- 6
- pages
- 620 - 652
- publisher
- Wiley
- external identifiers
-
- pmid:37329269
- scopus:85161960246
- ISSN
- 0007-9235
- DOI
- 10.3322/caac.21785
- language
- English
- LU publication?
- yes
- id
- ab89be12-9718-4381-a3b3-1fc2d055fa46
- date added to LUP
- 2023-10-30 11:20:27
- date last changed
- 2024-04-19 04:03:33
@article{ab89be12-9718-4381-a3b3-1fc2d055fa46,
abstract = {{<p>Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.</p>}},
author = {{Megyesfalvi, Zsolt and Gay, Carl M. and Popper, Helmut and Pirker, Robert and Ostoros, Gyula and Heeke, Simon and Lang, Christian and Hoetzenecker, Konrad and Schwendenwein, Anna and Boettiger, Kristiina and Bunn, Paul A. and Renyi-Vamos, Ferenc and Schelch, Karin and Prosch, Helmut and Byers, Lauren A. and Hirsch, Fred R. and Dome, Balazs}},
issn = {{0007-9235}},
keywords = {{chemotherapy; diagnosis; immunotherapy; molecular subtypes; small cell lung cancer}},
language = {{eng}},
number = {{6}},
pages = {{620--652}},
publisher = {{Wiley}},
series = {{CA: a cancer journal for clinicians}},
title = {{Clinical insights into small cell lung cancer : Tumor heterogeneity, diagnosis, therapy, and future directions}},
url = {{http://dx.doi.org/10.3322/caac.21785}},
doi = {{10.3322/caac.21785}},
volume = {{73}},
year = {{2023}},
}