Drug resistance biomarker could improve cancer treatment

November 21, 2012

Cancer therapies often have short-lived benefits due to the emergence of genetic mutations that cause drug resistance. A key gene that determines resistance to a range of cancer drugs has been reported in a study published by Cell Press November 21st in the journal Cell. The study reveals a biomarker that can predict responses to cancer drugs and offers a strategy to treat drug-resistant tumors based on their genetic signature.

"We need to understand the mechanisms of drug resistance to effectively prevent it from occurring in the first place," says senior study author René Bernards of the Netherlands Cancer Institute. "We have identified a mechanism of drug resistance that is caused by the activation of a specific signaling pathway in cancer cells."

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and NSCLC patients with a specific type of tumor mutation can be treated with a targeted therapy called crizotinib. But these patients frequently develop drug resistance as a result of secondary mutations in their tumors, through unknown genetic mechanisms.

To gain insight into this question, Bernards and his team developed a screen to identify genes whose suppression confers resistance to crizotinib in NSCLC cells. They discovered that inhibition of MED12, a gene that is mutated in cancers, resulted in resistance to not only crizotinib, but also other targeted drugs and chemotherapy used to treat various types of cancer.

The researchers also found that MED12 suppression caused drug resistance by enhancing signaling through the transforming growth factor beta receptor (TGF-betaR)--a protein involved in cell growth and cell death. By inhibiting TGF-betaR signaling in MED12-deficient cells, they were able to restore drug responsiveness. The results suggest that TGF-betaR inhibitors, which are currently being tested in clinical trials, may counter drug resistance in cancer patients with MED12 mutations.

"We have shown that blocking this escape route restores sensitivity to the original drug, suggesting a way to treat patients that have undergone this type of drug resistance." Bernards says.
-end-
Huang et al.: "MED12 controls the response to multiple cancer drugs through regulation of TGFbeta receptor signaling"

Cell Press

Related Lung Cancer Articles from Brightsurf:

State-level lung cancer screening rates not aligned with lung cancer burden in the US
A new study reports that state-level lung cancer screening rates were not aligned with lung cancer burden.

The lung microbiome may affect lung cancer pathogenesis and prognosis
Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer, according to results from a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

New analysis finds lung cancer screening reduces rates of lung cancer-specific death
Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening.

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.

Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.

Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.

Read More: Lung Cancer News and Lung Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.