Small-cell lung cancer: What we know, what we need to know and the path forward

Research output: Contribution to journalReview article

95 Citations (Scopus)

Abstract

Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

Original languageEnglish (US)
Pages (from-to)725-737
Number of pages13
JournalNature Reviews Cancer
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Small Cell Lung Carcinoma
Lung Neoplasms
Neoplasms
Therapeutics
Heterografts
Clinical Trials
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Small-cell lung cancer : What we know, what we need to know and the path forward. / Gazdar, Adi F.; Bunn, Paul A.; Minna, John D.

In: Nature Reviews Cancer, Vol. 17, No. 12, 01.12.2017, p. 725-737.

Research output: Contribution to journalReview article

@article{4f8c2b9e01424627ad8870bcf5adb66b,
title = "Small-cell lung cancer: What we know, what we need to know and the path forward",
abstract = "Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15{\%} of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.",
author = "Gazdar, {Adi F.} and Bunn, {Paul A.} and Minna, {John D.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/nrc.2017.87",
language = "English (US)",
volume = "17",
pages = "725--737",
journal = "Nature Reviews Cancer",
issn = "1474-175X",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Small-cell lung cancer

T2 - What we know, what we need to know and the path forward

AU - Gazdar, Adi F.

AU - Bunn, Paul A.

AU - Minna, John D.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

AB - Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

UR - http://www.scopus.com/inward/record.url?scp=85034813206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034813206&partnerID=8YFLogxK

U2 - 10.1038/nrc.2017.87

DO - 10.1038/nrc.2017.87

M3 - Review article

C2 - 29077690

AN - SCOPUS:85034813206

VL - 17

SP - 725

EP - 737

JO - Nature Reviews Cancer

JF - Nature Reviews Cancer

SN - 1474-175X

IS - 12

ER -