In a first, PGI Chandigarh develops liquid biopsy technique to detect oral cancer early

HOW DOES THE DIAGNOSIS TECHNIQUE WORK?

Working for over a decade, the research team started exploring individual candidate bio-molecules and over time, to improve drawbacks, started working on an approach of evaluating multiple molecules simultaneously. “We searched the literature and found saliva could be a good diagnostic fluid in OSCC as a collection of saliva does not require even a needle prick. We have chosen proteins one by one to ascertain their role in cancer pathophysiology. Cornulin, a down-regulated protein, was relatively unexplored and found to be significantly low in the saliva of patients. The tissue Cornulin was inversely correlated with the grading of the tumour. Lower salivary Cornulin levels also successfully predicted the outcome of the patients: the lower the level, the earlier the death. Our finding has been published in the Journal of Clinical Pathology,” says Prof Pal.

In the absence of a method for facility for isolating CTCs, Prof Pal and his team developed a novel in-house strategy which is awaiting a patent. Approximately 71 per cent (45/63) patients recruited in the study were CTC-positive and Overall Survival (OS) and Disease-Free Survival (DFS) were less in CTC-positive patients. Identification of CTCs in the blood of the patients and their association with prognosis will definitely open new avenues for personalised systemic therapy based on CTC-gene expression, new throughout the world and certainly a first in India.

Part of this gene expression study was conducted in collaboration with the National Institute of Biomedical Genomics, Kalyani, West Bengal, an autonomous institute under the Department of Biotechnology, Government of India. “Currently we are doing this at an experimental level and soon it will be available for patient care after required regulatory approvals,” explains Prof Pal.

WHY IS LIQUID BIOPSY IMPORTANT

A non-invasive technique for diagnosis much before standard clinical examination or radiological evidence improves treatment planning. It can be used to monitor disease recurrence after therapy, when the primary tumour has already been removed and cannot be biopsied again.

Depending upon the molecular types or characteristics of the CTCs found during the liquid biopsy, personalised therapies like immunotherapy or specific chemotherapy may be planned. This will improve the treatment response.

THIS TEST IS COST-EFFECTIVE

“The real value of our work will be established when we are able to use these advancements for humanity and give suffering cancer patients a better quality of life,” says Dr Pal. The test is cost-effective because it involves a non-invasive technique that does not require specific equipment and is not very technically challenging. Besides, it has been developed in-house. The initial funding for the project was from PGI. Now the Indian Council of Medical Research (ICMR) has approved a grant to the team and department to develop the test for patient care. Liquid biopsy, adds Prof Pal, is not widely available in India because of the high cost and non-availability of specialised instruments.

The scalable strategy, he adds, is suitable for many downstream applications and multiple cancers. “Its use in oral cancer may be expanded to other solid tumours just by changing identification markers easily. This will soon be available for regular patient care after regulatory diagnostic trials. We hope in one year, we can give this precious gift to humanity and save many lives,” says Prof Pal.

HOW THIS CAN IMPROVE ORAL CANCER OUTCOMES IN INDIA

Oral cancer, says Prof Pal, refers to any cancerous tissue growth within the oral cavity. Ninety per cent of these are Squamous Cell Carcinoma (OSCC). “Oral cancer is the sixth most common cancer around the world, with an annual estimated incidence of around 300,000 globally. Sixty two per cent of OSCC cases occur in developing countries. It is the third most occurring cancer in India with an incidence rate of 80,000 cases per year. The developing world with a relatively low income bears the maximum burden of OSCC. So, it has become a major healthcare problem in Low or Middle-Income Countries (LMICs), including India. Tobacco smoking, smokeless tobacco (betel quid, oral snuff), areca nut, alcohol, genetic factors, HPV infection and chronic trauma are the various risk factors,” says Prof Pal.