Abstract |
The impressive clinical activity of small-molecule receptor tyrosine kinase inhibitors for oncogene-addicted subgroups of non-small-cell lung cancer (for example, those driven by activating mutations in the gene encoding epidermal growth factor receptor (EGFR) or rearrangements in the genes encoding the receptor tyrosine kinases anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1) and rearranged during transfection (RET)) has established an oncogene-centric molecular classification paradigm in this disease. However, recent studies have revealed considerable phenotypic diversity downstream of tumour-initiating oncogenes. Co-occurring genomic alterations, particularly in tumour suppressor genes such as TP53 and LKB1 (also known as STK11), have emerged as core determinants of the molecular and clinical heterogeneity of oncogene-driven lung cancer subgroups through their effects on both tumour cell-intrinsic and non-cell-autonomous cancer hallmarks. In this Review, we discuss the impact of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer and assess the challenges and opportunities that co-mutations present for personalized anticancer therapy, as well as the expanding field of precision immunotherapy.
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Authors | Ferdinandos Skoulidis, John V Heymach |
Journal | Nature reviews. Cancer
(Nat Rev Cancer)
Vol. 19
Issue 9
Pg. 495-509
(09 2019)
ISSN: 1474-1768 [Electronic] England |
PMID | 31406302
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
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Chemical References |
- KRAS protein, human
- MAS1 protein, human
- Proto-Oncogene Mas
- TP53 protein, human
- Tumor Suppressor Protein p53
- EGFR protein, human
- ErbB Receptors
- Protein Serine-Threonine Kinases
- STK11 protein, human
- AMP-Activated Protein Kinase Kinases
- Proto-Oncogene Proteins p21(ras)
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Topics |
- AMP-Activated Protein Kinase Kinases
- Algorithms
- Animals
- Carcinoma, Non-Small-Cell Lung
(genetics, therapy)
- Disease-Free Survival
- ErbB Receptors
(genetics)
- Genome, Human
- Humans
- Immunotherapy
(methods)
- Lung Neoplasms
(genetics, therapy)
- Mice
- Mutation
- Oncogenes
- Phenotype
- Prognosis
- Protein Serine-Threonine Kinases
(genetics)
- Proto-Oncogene Mas
- Proto-Oncogene Proteins p21(ras)
(genetics)
- Tumor Suppressor Protein p53
(genetics)
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