Study shows how resistance to chemotherapies may occur in some cancers

New Delhi, Mar 29: US researchers have found how resistance to chemotherapies may occur in some cancers, an advance that could help pinpoint treatment-resistant tumours.

Chemotherapy resistance is a major challenge in cancer treatment. It occurs when cancer cells stop responding to chemotherapy, allowing the tumour to grow again.

The team from Mass General Brigham focused on a pathway that harnesses reactive oxygen species (ROS) to kill cancer cells. The study, published in the journal Nature, found that mutations to VPS35 -- a key player in this pathway -- can prevent chemotherapy-induced cell death.

“ROS play an important role in healthy and diseased cells, but pathways that sense and control cellular ROS levels are not well understood,” said corresponding author Liron Bar-Peled, of the Krantz Family Center for Cancer Research at the hospital.

“A clearer understanding of ROS could help us understand why chemoresistance occurs in some cases.”

Low concentrations of ROS are required for normal cell signalling, but higher levels of ROS can damage cells and contribute to diseases such as cancer and neurodegeneration.

Previous studies have shown that mitochondria play an important role in ROS production, but it has been unclear if ROS-sensing proteins influence the mitochondria. If they do, this could impact responses to some anti-cancer treatments.

To investigate the team screened cancer cells for ROS-sensing proteins that might contribute to chemoresistance.

They identified mutations that increased treatment resistance, and the team traced two of them to a protein called VPS35. Further studies showed that these mutations led to lowered ROS levels within the cell.

In addition, they analysed VPS35 expression levels in 24 patients with high-grade serous ovarian cancer (HGSOC), who received treatment at MGCC. They noted that higher tumoral VPS35 levels were associated with improved treatment responses and overall survival rates.