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Repurposing FDA-Approved Drugs for Novel Cancer Interventions

repurposing fda approved drugs for cancer

08/04/2025

Revisiting FDA-approved drugs can unmask potent anti-cancer activities, offering clinicians a faster route to novel interventions in colorectal and hepatocellular carcinoma.

Despite incremental advances in colorectal cancer treatment, outcomes for advanced-stage disease remain suboptimal (5-year survival for metastatic cases is approximately 15%), and hepatocellular carcinoma frequently shows limited response rates to first-line therapies. Drug repurposing oncology harnesses the established safety profiles and pharmacokinetics of existing compounds to fill these therapeutic gaps without starting from scratch.

Menadione colorectal cancer studies now suggest that this vitamin K3 analogue engages the MAPK8 (also known as JNK1) pathway to orchestrate apoptosis, necroptosis (a regulated form of necrotic cell death) and autophagy-associated cell death (cell death involving self-digestion pathways). A detailed mechanistic analysis of menadione’s induction of programmed cell death revealed that MAPK8 activation is central to its multi-pronged cytotoxicity, redefining the therapeutic potential of this off-patent molecule.

Expanding on these insights, network pharmacology platforms have mapped drug–target interactions to new oncologic indications. In hepatocellular carcinoma, computational docking and molecular dynamics simulations identified histone deacetylase 3 (HDAC3) as a high-affinity target of Nirmatrelvir. These in silico docking results are preliminary and should be validated by biochemical binding assays and cellular studies to confirm HDAC3 inhibition.

For clinicians designing early-phase trials, repurposing FDA-approved drugs offers substantial potential to shorten development timelines. As noted in the earlier screening of drug libraries, leveraging known toxicity data and established dosing guidelines compresses the timeline for clinical translation. Integrating repurposed candidates into combination regimens or biomarker-driven cohorts may unlock new avenues for patients refractory to standard treatments.

Key Takeaways:

  • Menadione presents a novel pathway for colorectal cancer treatment through MAPK8-induced programmed cell death.
  • Network pharmacology highlights Nirmatrelvir’s potential in treating hepatocellular carcinoma by targeting HDAC3.
  • Repurposing FDA-approved drugs offers a rapid and cost-effective path to developing new cancer therapies.
  • The repurposing approach is reshaping cancer treatment paradigms, reducing time from bench to bedside.

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