Study could pave way for better oral cancer treatment

New Delhi: Oral cancer is one of the considerable public health burdens. In India, the concern is higher as most oral cancer cases are diagnosed in advanced stages. Researchers from the National Institute of Biomedical Genomics (NIBMG), Kalyani, West Bengal, have explored the possibilities for targeting drug-tolerant Cancer Stem Cells (CSCs) to discover new avenues for treating oral cancer.

Among all cancer cells, specific subsets of cancer cells play crucial roles in cancer initiation, progression, and therapy resistance. These subsets of cells have stem-cell-like properties of long-term tissue repair and regeneration and are known as CSCs.

“We have evolved a strategy to target the mechanism of drug resistance in oral cancer cells. The main barrier against targeting cancer cells is their ability to change their state and attain CSC-like properties to escape therapeutic stress and demonstrate drug resistance. Therefore, the study aimed to identify possible targets against cellular plasticity and drug-refractory mechanisms in oral cancer cells,” informs Dr Sandeep Singh, the lead researcher.

Approximately 35% of oral cancer patients with surgically removed primary tumours develop loco-regional secondary and/or metastatic disease within 2.5 years. Recurred cancers show very aggressive features and extremely poor post-recurrence survival of the patients. Re-irradiation or chemotherapy remains the only option for relapsed oral cancer salvage surgery.

“Our study is based on the earlier reported observations where the NOTCH gene has been found to have both loss or gain of function status among oral cancer patients. We have explored the possibility of a ‘synthetic lethal approach’ to identify target genes on which CSCs are co-dependent for survival,” Dr Singh mentions.

According to the study team, there was an urgent need to identify the mechanism of drug tolerance in oral cancer cells to overcome therapy resistance. Targeting CSCs in cancer cells is suggested to be the most logical approach for novel drug discovery.

“In our study, oral CSCs showed chemotherapy resistance by gaining the NOTCH function, while inhibition of this resulted in more aggressive tumour growth. Therefore, results suggested that NOTCH acts as a double-edged sword in oral cancer with bimodal action,” the researchers inform India Science Wire.

The team successfully found a small set of genes as a signature that could segregate oral cancer patients into different prognostic groups. It was discovered that patients having inactive-NOTCH showed poorer prognoses.

“Targeting the NOTCH-inactive population could provide a better outcome,” the researchers contemplate.

The gene signature obtained from the study can be used to identify patients who may have a poorer prognosis. However, the discovered biomarker must be validated in a larger patient cohort, especially from the Indian population, before the discovery gets translated to the clinic for the benefit of the patients.

Besides Dr Sandeep Singh, the team consists of Subhashis Ghosh, Paromita Mitra, Uday Saha, Rimpa Nandi, Subhashree Jena, Arnab Ghosh, Shantanu Saha Roy, Moulinath Acharya, and Nidhan Kumar Biswas. The article has been published in Translational Oncology. The study has been funded by DST-SERB, Govt. of India, and the NIBMG intramural core grant.

(India Science Wire)