Some scientists at Nanyang Technological University in Singapore report that certain existing cancer drugs can be repurposed to target a subset of cancers that lack targeted treatment options, specifically glioblastomas. The study published in Nature Communications shows that the drug ponatinib (approved for the treatment of bone marrow cancer) prevents certain cancer cells from proliferating indefinitely in cell experiments and mouse tests. Ponatinib can impede the alternative lengthening of telomeres (ALT) mechanism through which these cancers attain immortality, leading to cancer cell death.
According to the scientists, 15% of cancer types elongate their telomeres through alternative means, classifying them as "telomerase-positive cancers." Dr. Maya Gaitani, a member of the research team, explained that a prominent feature of cancer is its ability to evade cell death and achieve unlimited proliferation to remain immortal, which it accomplishes via the ALT mechanism. While a large portion of cancer cells relies on this mechanism, there is currently no clinically approved targeted treatment.
Dr. Gaitani added, "Through our study, we identified a new signaling pathway in the telomere elongation mechanism and demonstrated that the FDA-approved drug ponatinib inhibits this pathway and shows exceptional promise in stopping the growth of cancer cells with alternative telomere lengthening. Our findings could provide a new direction for treating ALT-positive cancers by repurposing an FDA-approved drug for these tumor types."
The scientists identified the potential use of ponatinib for treating ALT-positive cancers through high-throughput screening, where they analyzed a large number of biological and pharmaceutical compounds, followed by hands-on testing of a shortlist of drugs. The team found that when they treated cells from osteosarcoma and liposarcoma (a type of tumor that grows in adipose tissue) with ponatinib in the lab, the cells suffered DNA damage, telomere dysregulation, and eventually ceased to divide. Furthermore, it was observed that telomere production decreased within 18-20 hours after administering the drug to the cells.
Dr. Gaitani and her colleagues also noted that in experiments conducted on mice implanted with human cancer cells, treatment with ponatinib reduced tumor size without affecting the rodents' body weight, which is a common side effect of cancer treatments. Professor and oncologist Valeria Yang commented, "Sarcoma and glioblastoma are highly complex cancers that are more prevalent among young individuals and currently have limited treatment options. Identifying an FDA-approved drug that can be repurposed to target the alternative lengthening of telomeres, a vulnerability in these cancers, is very exciting."
