NTU Singapore scientists discovered the potential for modifying cancer medicine to target specific types of cancer, addressing limited treatment options.

Researchers at NTU Singapore discovered that cancer medicine can target specific cancer groups, including aggressive osteosarcomas and glioblastomas, which have limited treatment options and poor outcomes. This discovery holds promise for improved treatments.

Ponatinib, an approved cancer drug, inhibits the alternative lengthening of telomeres (ALT) process, shrinking tumors without weight loss and reducing ALT cancer marker levels in mice treated with the drug.

Progress has been made in finding a targeted treatment for ALT cancers, which currently lack approved therapies. Dr. Maya Jeitany and her team from NTU School of Biological Sciences, collaborating with researchers from the Cancer Science Institute and Yong Loo Lin School of Medicine at NUS and the Genome Institute of Singapore at A*STAR, are jointly addressing this challenge.

Dr. Jeitany, the lead researcher, revealed that cancer cells avoid death and keep multiplying through “alternative lengthening of telomeres” (ALT). Despite its prevalence, there is no approved targeted therapy for this mechanism. However, their study identified a new signaling pathway in ALT and found that the FDA-approved drug ponatinib can effectively block it, showing potential for halting the growth of ALT cancer cells. This discovery opens the possibility of repurposing ponatinib as a treatment option for ALT cancers, utilizing an existing FDA-approved drug for these tumor types.

Researchers have discovered a promising approach for treating ALT cancers using an FDA-approved drug meant for a different cancer type. Assistant Professor Valerie Yang, a medical oncologist, finds this discovery exciting because ALT cancers, such as sarcomas and glioblastomas, have limited treatment options, particularly for young patients.

ALT cancers, accounting for 15% of all cancers, use an alternative method called "alternative lengthening of telomeres" to sustain their cells. Normal telomeres shorten with cell division, but cancer cells activate telomerase, allowing limitless multiplication.

Currently, no approved targeted treatment exists specifically for ALT cancers, and certain types like osteosarcoma and glioblastoma show poor responses to chemotherapy. However, researchers found that ponatinib, an FDA-approved drug for bone marrow cancer, effectively kills ALT cancer cells. This discovery holds promise for future ALT cancer treatments.

When used to treat osteosarcoma and liposarcoma (fatty tissue tumors), ponatinib caused DNA damage and affected telomeres, leading to cell senescence and halting division. After 18 to 20 hours of treatment, telomere production in the cells also decreased.

Ponatinib treatment caused DNA damage and affected telomeres in osteosarcoma and liposarcoma cells, leading to cell senescence and halting division. After 18 to 20 hours, telomere production decreased.

In mouse tests with transplanted human bone cancer cells, ponatinib effectively reduced tumor size without inducing weight loss – a common side effect of cancer treatments. This indicates ponatinib’s potential as a treatment for these cancers.