Snake venom-derived peptides as anticancer candidates: Pioneering next-generation therapies

Cancer treatment has come a long way, but not all cancers can be completely cured. The current therapeutic landscape has significantly reduced mortality rates; however, it remains associated with side effects, limited accessibility, financial burden, drug shortages, and emotional as well as mental health consequences for patients. Hence, despite significant advances, the development of novel therapies remains a focal point of research. In this review, we explore the current state of snake venom-inspired peptides as templates for the design of much-needed innovative anticancer agents. Initially, we examine conventional cancer treatments, their main challenges, and the niche filled by newly approved peptide-based therapies. Then, we present a high-level overview of the potential of snake venoms as broad-spectrum libraries of bioactive components and discuss a roadmap for mining these rich and complex mixtures to pioneer the next generation of cancer drugs, leading to the emergence of "oncovenomics". Harnessing the potential of modern in silico approaches, we delve into the structure, biochemical parameters, and bioactivity of venom-inspired peptides. Our research identified more than 30 snake venom-derived peptides with micromolar lytic action against different cancer cells, including solid and liquid tumours. Transitioning from in vitro monolayer analyses to clinical settings remains an unfulfilled goal, with the majority of studies failing to progress to more advanced stages, including the preclinical phase involving in vivo experiments. Here, we also describe how artificial intelligence, and the integration of other cutting-edge technologies can provide an expandable framework for translating the high in vitro potential of venom-derived peptides into clinically useful therapies. Lastly, we examined the translational challenges and the strategies proposed to overcome them. In summary, snake venom-derived peptides are attractive scaffolds for drug discovery programs, demonstrating historical benefits. However, overcoming the existing barriers in their development requires further multidisciplinary efforts. On the horizon, advances in high-throughput research tools and peptide engineering strategies offer opportunities for introducing next-generation venom peptide-based therapeutics to address cancer in clinical practice.