Scientists at the National Institute of Biomedical Genomics, Kalyani, have identified genetic mechanisms that drive the transformation of normal cells into cancerous oral tumours, a finding that they say could lead to novel cancer treatment strategies.

Cancer biologist Nidhan Biswas and his colleagues at the NIBMG have found that mutations in a gene that makes a protein called Caspase-8 initiate the changes in oral tissues towards an abnormal condition called leukoplakia and then into cancer.

“Changes in the Caspase-8 gene trigger the malignant transformation of a benign leukoplakia lesion into cancer,” said Biswas.

“It is a stepwise process: the changes in Caspase occur first, then the cells accumulate mutations in other cancer-linked genes, culminating in the malignancy.”

Oral cancer is the commonest cancer among men in India and is linked to tobacco chewing. Cancer-causing agents in tobacco damage cells in the oral cavity, causing genetic changes. Doctors have known for years that most oral cancer lesions are preceded by white patches called leukoplakia.

Medical studies in the past have suggested that about 9 per cent of people with leukoplakia tissues acquire genetic changes leading to malignant tumours. Doctors typically ask leukoplakia patients to return for follow-up visits every six to 12 months to look out for progression towards cancer.

The NIBMG researchers collaborated with doctors at the R. Ahmed Dental College and Hospital, Calcutta, to study DNA or genetic material from three types of tissues from patients – normal, cancerous and leukoplakic.

The study is the first to determine the stepwise genetic changes and molecular mechanisms that underlie the transformation of cells towards malignancy.

“Our work opens up the theoretical possibility of using immunotherapeutic or other drugs to prevent precancerous cells from gaining additional abnormal changes to eventually form cancer,” said Partha Majumder, distinguished professor at the NIBMG and senior co-author of the study.

“We asked ourselves — can we identify some key changes in the DNA of cells in leukoplakia tissue that trigger the formation of frank (manifest) oral cancer?” he added.