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.
N1 - Funding Information:
This work was supported by grants from the National Cancer Institute, Bethesda, Maryland, USA: ‘Specialized Program in Research Excellence in Lung Cancer’, P50 CA70907 and the ‘Small Cell Lung Cancer Consortium Coordinating Center’ U24CA213274 (A.F.G. and J.D.M.) and the ‘Colorado Lung Cancer SPORE’ P50-CA058187 (P.A.B.).
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.
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U2 - 10.1038/nrc.2017.87
DO - 10.1038/nrc.2017.87
M3 - Review article
C2 - 29077690
AN - SCOPUS:85034813206
SN - 1474-175X
VL - 17
SP - 725
EP - 737
JO - Nature Reviews Cancer
JF - Nature Reviews Cancer
IS - 12
ER -