Targeting glioblastoma multiforme through a multifaceted therapeutic drug approach

Being the most aggressive primary brain tumor in adults Glioblastoma multiforme (GBM) represents a formidable challenge for clinicians. Despite multifaceted treatment strategy encompassing surgical intervention, radiation therapy, and chemotherapy, the prognosis for GBM patients remains dismal, with a median survival of just 14.6 months. Temozolomide (TMZ), the standard chemotherapy followed by bevacizumab, offers only a marginal improvement, extending median survival by a mere 2.5 months. It's evident that more effective treatments for GBM are urgently required. In a recent breakthrough, one of our novel cyclic peptide, has shown remarkable promise. By selectively inhibiting the activity of sPLA₂IIA an inflammatory phospholipase enzyme, our drug can significantly inhibit GBM cell proliferation at higher efficacy compared to TMZ (in multiple GBM cell lines including T98G cell line resistant to TMZ therapy. Our drug surpassed TMZ in inhibiting the growth of our 3D GBM tumoroids, which further supports the potential of our drug to inhibit tumour growth compared to TMZ. Importantly our drug is shown to reach rodent brain post oral and intraperitoneal administration of our-drug confirming its ability to cross blood brain barrier. Importantly our drug is found to be more potent than TMZ in inhibiting wound healing of GBM cell lines suggesting its role in inhibiting cell migration and thus metastases. Further to dissect the mechanism of its action as an anti-GBM candidate we performed a high throughput proteomic analysis of GBM cell lines treated with our drug, TMZ and placebo. We have identified 2673 proteins in total in which 43 were significantly down regulated and 103 are significantly upregulated when GBM cells treated with our drug candidate. All together, these proteins regulate a diversity of cancer-related signalling networks and cellular functions This work represents a promising development in the field of GBM therapeutics.

Dr. Shadma Fatima is a molecular biologist specializing in precision medicine, immunology, and bioinformatics, with expertise in omics-driven cancer biomarker and drug discovery. Earning her Ph.D. from Monash University in 2017, she pioneered discoveries on BRAP2 and Imp13 in mammalian development. She leads the world’s first study on Secretory Phospholipase A2 in brain cancer, developing novel drugs and diagnostics that outperform standard treatments. Her innovations span glioblastoma, prostate cancer, and COVID-19 therapies. Recognized with multiple awards, Dr. Fatima is a published researcher, educator, and mentor, driving interdisciplinary collaborations to advance targeted therapies and non-invasive diagnostics in oncology and beyond. Her research has attracted over $1.7M across academic research and industry-based project grants. She has co-authored more than 25 publications in prestigious venues—e.g., Briefing in Bioinformatics (IF: 13.99), Cancers (IF  6.69), FASEB (IF: 5.834), Nature Sc Reports (IF: 4.996) Frontiers in nutrition (IF 7.8) demonstrating her research impact, leadership, and substantive contribution in advancement of research.