The researchers have developed a different attack strategy to tackle glioblastoma—an aggressive form of brain: Getty Images/File)Researchers at the IIT Gandhinagar (IITGN) have developed a different attack strategy to tackle glioblastoma—an aggressive form of brain cancer that is resistant to a commonly used chemotherapy drug.In their paper published in the Journal of Biological Chemistry and RSC Medicinal Chemistry, the researchers said two compounds developed by them suppressed the growth of glioblastoma cells by blocking a protein’s activity that regulates cell division.The two compounds can target tyrosine threonine kinase (the TTK or Mps1 protein), which is integral to cell division, they argued. High levels of this protein have been linked to glioblastoma progression.“Since cancer cells divide at a much faster rate than normal cells, they rely heavily on TTK to survive their chaotic division cycles. The researchers asked whether disrupting this checkpoint could make it harder for glioblastoma cells to manage the damage to their DNA. It can reduce their viability and enhance their sensitivity to treatments like radiotherapy. Earlier studies have linked TTK’s involvement in resistance to TMZ, a commonly used chemotherapy drug. We wanted to explore whether modifying a candidate from one of our previous studies, J54 (a selective inhibitor of TTK), could help us target TTK more effectively and guide further research into ways of tackling drug-resistant glioblastoma,” the first author of this study, Gaurav Rai, a PhD scholar of the Chemistry Department at IITGN and a recipient of the Prime Minister’s Research Fellowship, told The Indian Express.The studies revealed that less SPK17 and SPK17b-the two molecules derived from anti psychotics that act on central nervous system-are more effective compared to the routine chemotherapeutic drug.“The current standard-of-care involves the use of temozolomide (TMZ), a chemotherapy medication. However, the tumour can be difficult to control because cancer cells evolve to evade the effects of such treatments. Thus, finding new ways to target these cells is an important area in cancer research,” Rai added.Second author of the other study, Deepika Khasa, added, “We also realised that SPK17b appeared to do more than slow the growth of glioblastoma cells. The treated cells showed an impaired ability to metastasise or spread, one of the hallmarks of cancer.” Deepika is also a PhD student in the Chemistry Department at IITGN.Story continues below this adTogether, these results suggest that the two compounds may interfere with several processes that help tumour cells survive and multiply.Explaining the mechanism involved, Gaurav said, “Both compounds act on the same protein—TTK, but the two studies followed different consequences of blocking it. SPK17 removes a built-in pause that normally gives a dividing cell time to mend its damaged DNA. The cell is pushed through division with the damage unrepaired, and it accumulates until the cell dies. SPK17b instead causes a build-up of reactive oxygen species, toxic by-products of the cell’s own metabolism, until the cell’s defences are overwhelmed and it self-destructs, while also leaving surviving cells less able to move and invade surrounding tissue.”According to Prof Sivapriya Kirubakaran, “When you are working on a disease as aggressive as glioblastoma, you are aware of how urgently better treatment options are needed. Findings like those from our study can bring us closer to asking the right questions to improve understanding of difficult diseases. Our two compounds give us a mechanism-based therapeutic strategy to investigate how we might target drug-resistant tumour cells. Future studies to understand the efficacy of the molecules in animals are ongoing.” Professor Kirubakaran is the Kankuben Bakshirambhai Gelot Chair Professor in the Chemistry Department at IITGN and heads the Cancer Chemical Biology lab at the Institute.“The next step should be to establish whether the candidate is effective in progressively complex biological systems and whether its benefits outweigh its risks.”Ritu Sharma is an Assistant Editor with The Indian Express' Gujarat bureau, an editorial position th... Read More Tags:brain tumour