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Irinotecan + rapamycin is a combination therapy that targets multiple pathways in cancer cells. This combination specifically targets the mTOR/HIF-1α axis, with rapamycin inhibiting the mammalian target of rapamycin (mTOR) and irinotecan inhibiting topoisomerase I and preventing the accumulation of HIF-1α. Studies have shown that this combination demonstrates synergistic effects in various cancer models, particularly in colon cancer and pancreatic cancer. The combination has shown potent inhibition of tumor growth in xenografted models, with dramatic reduction in tumor volume compared to single-agent therapy. In hypoxic conditions, the combination induces massive cancer cell death, suggesting its effectiveness is mediated through HIF-1α inhibition rather than through genotoxic lesions.
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