Cancer Mutation Improves Chemo Drug Performance

When it comes to cancer biomarkers, it’s often the genetic signatures that are associated with poor patient outcomes that take center stage. Take for example triple-negative breast cancer, a diagnostic marker for a condition that is notoriously difficult to treat and puts patients at significantly higher risks of relapse after therapy.

A team of cancer researchers based at the Terry Fox Research Institute have identified a gene mutation in lymphoma that serves as a biomarker for the opposite — it’s associated with improved patient survival instead.

Scientists David Scott and Christian Steidl led the study which was published in Nature Medicine. Here, they describe that patients with Diffuse Large B-cell Lymphoma, or DLBCL that lack a particular protein called TMEM30A are actually more susceptible to chemotherapeutic drugs, leading to better outcomes.

Shannon Healy, the first author of the paper said, “In contrast to most studies that describe gene mutations associated with poor survival, we observed that DLBCL cells with complete loss of TMEM30A actually showed increased uptake of cytotoxic drugs, most notably those that are used to treat DLBCL, such as doxorubicin and vincristine.”

DLBCL is the most common type of non-Hodgkin lymphoma worldwide. In the United States, almost 20,000 people are diagnosed with this aggressive cancer annually. It affects a particular subset of immune cells called B-lymphocytes which produce antibodies to resist infections.

The team’s discovery sheds light on why some cancer patients respond much more favorably to cytotoxic drugs than others. In the case of DLBCL, the research team believes that the TMEM30A mutation allows these cancer-killing drugs to pass through the cell membrane more efficiently. This could translate to a new generation of future therapeutics that target TMEM30A to shuttle the cytotoxic molecules into cancer cells.

Sources: Nature Medicine, The Terry Fox Research Institute.