A research team led by Manoj Pandey from the Department of Surgical Oncology at the Institute of Medical Sciences, Banaras Hindu University (BHU), has identified the somatic mutations responsible for developing gallbladder cancer.
Gallbladder cancer is one of the most common kind of cancers reported in the Gangetic belt. The cancer is often diagnosed late and has a poor survival rate. The current five-year survival rate is 10-20 per cent.
According to Pandey, the researchers at BHU have been working on gallbladder cancer for the past 25 years to find out the probable causes which continue to remain elusive.
As a part of the research, the team carried out next generation sequencing of tumour DNA from gallbladder cancer in 33 patients. This was further subjected to bioinformatics analysis.
The research team identified 27 somatic mutations that involved 14 critical genes. Of these, two genes namely p53 and KRAS were the most mutated and appeared to be driver mutations behind these cancers.
He said that the bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR and Focal Adhesion PI3K-AKT-mTOR signalling pathways and cross-talk between these pathways.
The study suggested that the complex crosstalk between the mTOR, MAPK and multiple interacting cells signalling cascades promotes gallbladder cancer progression, and hence, motor targeted treatment is an attractive option in the cure of gallbladder cancer.
These targeting molecules are available and approved for different indications, however, they have never been used in gallbladder cancer.
The findings of the study have been published in the prestigious scientific journal Molecular biology reports.
According to Pandey, the driver mutations for gall bladder cancers have been identified for the first time.
However, it is still unclear why the mutations occur mainly in these two genes in this geographical area. Heavy metal toxicity and typhoid carrier state have earlier been implicated in gallbladder carcinogenesis.
He said this pathway and the cross talk have been identified for the first time in the world, and this opens the gate for use of new therapeutic drugs like evrolimus and temsirolimus in gallbladder cancer. Both of these drugs are mTOR inhibitors and interfere with the synthesis of proteins that regulate proliferation, growth and survival of tumour cells.
They also reduce tumour growth by reducing angiogenesis (new blood vessel formation in tumour) by inhibiting VEGF (gene) and hence cut its food supply, thereby killing the cells.
Pandey added that the research team has submitted a proposal for a clinical trial of mTOR inhibitors in gallbladder cancer, which if successful, will open a new doorway for treatment of gallbladder cancer which is considered incurable till now.
