Researchers have discovered how mutations in the VPS35 protein can lead to chemotherapy resistance in certain cancers. The study highlights the role of reactive oxygen species (ROS) in cancer cell death and treatment response. Higher VPS35 levels were linked to better survival rates in ovarian cancer patients. These findings could help doctors predict which tumors may resist standard treatments.
March 31, 2025
Study shows how resistance to chemotherapies may occur in some cancers
"“A clearer understanding of
ROS could help us understand why chemoresistance occurs in some cases.” – Liron
Bar-Peled
Study shows how resistance to
chemotherapies may occur in some cancers
US researchers have found how
resistance to chemotherapies may occur in some cancers, an advance that could
help pinpoint treatment-resistant tumours.
Key Points
1 VPS35 mutations reduce ROS levels in cancer cells
2 Higher VPS35 linked to better ovarian cancer survival
3 Mitochondrial ROS pathways influence chemo response
4 Study could help identify resistant tumors early
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.
Subscribe to:
Post Comments (Atom)
No comments:
Post a Comment