Combining Repurposed Drugs with Precision Oncology: Studying synergistic effects of repurposed drugs with targeted therapies or immunotherapies.

By Editorial Team
Combining repurposed drugs with precision oncology—targeted therapies or immunotherapies—holds transformative potential by exploiting synergistic effects to improve efficacy, overcome resistance, and expand treatment options for rare and complex cancers.

Synergistic Mechanisms and Rationale

  • Multi-pathway targeting: Cancer’s genetic heterogeneity and signaling complexity often render single-agent targeted therapies insufficient. Repurposed drugs, many originally developed for non-oncologic indications, can complement targeted agents by hitting additional pathways or tumor microenvironment factors, reducing resistance and enhancing tumor control.

  • Low toxicity enabling combinations: Repurposed drugs typically have well-characterized safety profiles and lower toxicity, allowing their use in complex multi-drug regimens that target several oncogenic pathways simultaneously without excessive side effects. This multi-pronged approach can improve outcomes in cancers with limited options.

Examples and Evidence

  • The MEMMAT combination, involving repurposed drugs, showed promising activity in atypical teratoid rhabdoid tumors, illustrating how drug repurposing can augment precision oncology regimens.

  • Tamoxifen, originally a contraceptive, was repurposed as an estrogen receptor antagonist in breast cancer, exemplifying how mechanistic insights enable repurposed drugs to synergize with targeted treatments.

  • Auranofin, an anti-arthritic drug, demonstrated selective efficacy against gastrointestinal stromal tumors, including resistant cases, highlighting repurposed drugs’ potential to complement or overcome resistance to standard targeted therapies.

Computational and Experimental Advances

  • Computational methods such as molecular docking, network analysis, and machine learning enable the identification of repurposed drugs with mechanisms complementary to targeted agents or immunotherapies, facilitating rational combination design.

  • High-throughput phenotypic screening and omics-based signature matching help predict synergistic drug pairs by comparing drug-induced molecular changes with tumor-specific dysregulations.

Clinical and Global Impact

  • Combining repurposed drugs with precision oncology can expand the pool of actionable targets, especially important in rare cancers where approved targeted therapies are scarce.

  • This approach offers cost-effective treatment alternatives, making precision oncology more accessible globally, including in low- and middle-income countries where expensive novel agents may be unaffordable.

In summary, integrating repurposed drugs with targeted therapies or immunotherapies leverages complementary mechanisms and low toxicity profiles to achieve synergistic anti-cancer effects. Supported by computational tools and molecular profiling, this strategy enhances precision oncology’s reach and efficacy, particularly for rare and resistant cancers.

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