Gene variant makes head and neck cancer more aggressive

A genetic variant in a gene called MET is responsible for more aggressive growth of head and neck cancer, and lung cancer, according to a new study.

A further probe into the finding reveals therapeutic strategies that could potentially target this genetic alteration and pave the way for better and more effective treatments.

The MET gene encodes for a cancer promoting protein that relays growth, survival, and transmission of signals in cancer cells, researchers say.

As reported in Nature Communications, researchers also identified a form of MET protein which showed ethnic preference with higher incidence among Asians, and associated with poorer prognosis in patients diagnosed with head and neck squamous cell carcinoma or lung squamous cell carcinoma.

Even though the MET variant does not seem to predispose someone to head and neck cancer or lung cancer, it leads to more aggressive growth of cancers that have already developed.

Unlike other MET mutants, existing MET-blocking drugs do not seem to inhibit this genetic variant, prompting researchers to conduct further investigation on the mechanism behind the genetic alteration.

The team found that the single amino-acid change in the MET receptor from the genetic alteration leads to preferential strong binding to another cancer promoting protein, HER2. Both proteins then work together to drive cancer aggression and allow the cancer cells to survive therapies that involve MET-blocking drugs.

“The mechanism of this MET variant is novel and unreported. This finding contributes to the growing evidence of the role of genetic variants in affecting clinical outcome, and underscores the importance of diving deep into our genetic inheritance in cancer research,” says Kong Li Ren of the Cancer Science Institute (CSI) Singapore at NUS, who initiated the study.

Knowledge of this unique mechanism also allowed researchers to identify several HER2 inhibitors capable of blocking cancer progression the genetic alteration caused.

“Our study represents a conceptual advancement to cancer research, as we have shown that it is possible to block the activity of a cancer-driving gene by administrating a targeted therapy directed not against the mutant protein in question, but rather, a corresponding protein with which it binds to,” says Goh Boon Cher, deputy director and senior principal investigator at CSI Singapore.

“The remarkable anti-tumor responses observed in our experimental models, coupled with the availability of FDA-approved HER2 inhibitors, also presents a huge opportunity for clinicians to improve disease outcome of this genetic alteration via precision medicine.”

The research team is now translating the findings to a clinical trial where patients tested positive for this MET variant gene are treated with suitable medications that have shown effectiveness in the laboratory.

Additional coauthors are from the National University Cancer Institute, the National Cancer Centre Singapore, and the Bioinformatics Institute at the Agency for Science, Technology and Research, Singapore.

Source: National University of Singapore

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