Project Details

Overcoming the "Triad-of-Death" by Developing Frontier Anti-Cancer Drugs for Childhood Neuroblastoma

Mahendiran Dharmasivam, BSc, BEd, MSc, PhD

Summary

BACKGROUND: Every year >800 Australian children are diagnosed with cancer, resulting in 3 deaths/week. In the U.S.A. in 2021, it is estimated that 15,590 children will be diagnosed with cancer and 1780 will die (National Cancer Institute). Neuroblastoma is an aggressive extracranial childhood tumor, and unfortunately, the prognosis of advanced neuroblastoma remains poor, and breakthrough therapeutic approaches are urgently required. GAP: Neuroblastoma remains an aggressive and stubbornly resistant childhood cancer, with novel treatments being critical to develop. Over the past 36-years, my current lab has generated a substantial track record in developing a pipeline of innovative anti-cancer agents that overcome the deadly "Triad-of-Death" in cancer, namely metastasis, primary tumor growth, and resistance. No other group of anti-cancer agents possess all these three innovative properties. HYPOTHESIS: I hypothesize that via our specifically tailored structural changes, this 3rd-generation of PPPT agents will demonstrate potent and selective activity against neuroblastoma that markedly exceeds standard chemotherapy. METHODS: The 3rd -generation PPPT analogs will initially examine the in vitro anti-proliferative activity and followed by in vivo activity in several human neuroblastoma xenograft models. RESULTS: Pending. IMPACT: The impact will be an exciting new anti-cancer drug for aggressive neuroblastoma that overcomes the deadly Triad-of-Death, namely metastasis, primary tumor growth, and resistance. These studies are critical for the translation of the 3rd-generation PPPT analogs from bench-to-bedside and will take advantage of our extensive expertise in terms of anti-cancer drug development, licensing, and clinical trials. Website Link: https://cbdd.org.au/

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