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Small-cell lung cancer: what we know, what we need to know and the path forward
- Source :
- Nature Reviews Cancer. 17:725-737
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Ubiquitin-Protein Ligases
General Mathematics
Notch signaling pathway
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Animals
Humans
Medicine
Molecular Targeted Therapy
Lung cancer
Cytotoxic Therapy
Receptors, Notch
business.industry
Applied Mathematics
Cancer
medicine.disease
Neurosecretory Systems
Small Cell Lung Carcinoma
Xenograft Model Antitumor Assays
Cellular signal transduction
respiratory tract diseases
Clinical trial
Retinoblastoma Binding Proteins
030104 developmental biology
030220 oncology & carcinogenesis
Genetically Engineered Mouse
Non small cell
Tumor Suppressor Protein p53
business
Signal Transduction
Subjects
Details
- ISSN :
- 14741768 and 1474175X
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Nature Reviews Cancer
- Accession number :
- edsair.doi.dedup.....bfabebc02de1ab649cbfbe9247da7383