MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32913197.
- Also identified by DOI 10.1038/s41467-020-18372-1 and PMC identifier 7484793.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
Medical subject headings
- Antineoplastic Agents
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
- Myeloid Cell Leukemia Sequence 1 Protein