To date, cisplatin-based combination therapy is the standard of care for the treatment of small cell lung cancer (SCLC). Although most tumours initially respond excellent to this treatment, most patients will inevitably relapse within one year and will become resistant to cisplatin. Patients with platinum resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA-approved drug; irinotecan has an objective response rate of approximately 3% with little or no survival benefit. Therefore, agents that improve the anti-cancer activity of irinotecan would be of great value to these patients.
The natural compound capsaicin has been shown to have anti-cancer effects, but its heat can also cause a burning sensation, stomach cramps, gut pain and nausea. In new work, arvanil, a synthetic capsaicin analogue without capsaicin’s undesirable side effects, was studied for its potential synergism with irinotecan.
When two cisplatin-resistant lung cancer cell lines were exposed to low concentrations of arvanil, no growth-inhibitory activity was observed. However, when arvanil was combined with varying concentrations of irinotecan, the presence of arvanil greatly enhanced the inhibition of cancer cell growth. Caspase-3 activity assays reveal that the combination of irinotecan and arvanil displayed greater apoptotic activity in H69-CPR human cisplatin-resistant SCLC cells than the drugs used alone. These experiments were repeated in a second cisplatin-resistant lung cancer cell line PC9-CDDP and similar results were obtained. Statistical analysis showed that the interaction between arvanil and irinotecan was synergistic in nature in both cell lines. Moreover, the combination of arvanil-irinotecan showed a greater synergistic pro-apoptotic activity than the combination of capsaicin-irinotecan.
Taken together, these findings pave the way for the discovery of novel combination therapies for the therapy of cisplatin-resistant small-cell lung cancer.
Friedman J. The Synthetic Capsaicin-analog Arvanil sensitizes Cisplatin-Resistant Human Lung Cancer Cells to the pro-apoptotic activity of Irinotecan. Presented at Experimental Biology 2021; Poster R361.