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Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway performs a central role in tumorigenesis and is constitutively activated in many malignancies. As a novel dual PI3K/mTOR inhibitor currently undergoing evaluation in a phase I/II clinical trial, NVP-BEZ235 indicates a significant antitumor efficacy in diverse solid tumors, including colorectal cancer (CRC). Autophagy is a catabolic process that maintains cellular homeostasis and reduces diverse stresses through lysosomal recycling of the unnecessary and damaged cell components. This process is also observed to antagonize the antitumor efficacy of PI3K/mTOR inhibitor agents such as NVP-BEZ235, via apoptosis inhibition. In the present study, we investigated anti-proliferative and apoptosis-inducing ability of NVP-BEZ235 in SW480 cells and the crosstalk between autophagy and apoptosis in SW480 cells treated with NVP-BEZ235 in combination with an autophagy inhibitor. The results revealed that, NVP-BEZ235 effectively inhibit the growth of SW480 cells by targeting the PI3K/mTOR signaling pathway and induced apoptosis. The inhibition of autophagy with 3-methyladenine or chloroquine inhibitors in combination with NVP-BEZ235 in SW480 cells enhanced the apoptotic rate as componets to NVP-BEZ235 alone. In conclusion, the findings provide a rationale for chemotherapy targeting the PI3K/mTOR signaling pathway presenting a potential therapeutic strategy to enhance the efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with an autophagy inhibitor in CRC treatment and treatment of other tumors. [ABSTRACT FROM AUTHOR]

The booming photothermal therapy (PTT) has achieved great progress in non-invasive oncotherapy, and paves a novel way for clinical oncotherapy. Of note, mild temperature PTT (mPTT) of 42–45°C could avoid treatment bottleneck of the traditional PTT, including nonspecific injury to normal tissues, vasculature and host antitumor immunity. However, cancer cells can resist mPTT via heat shock response and autophagy, thus leading to insufficient mPTT monotherapy to ablate tumor. To overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT, synergistic therapies towards cancer cells have been conducted with mPTT. This review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment, including strategies for enhanced single-mode mPTT and mPTT plus synergistic therapies. Moreover, challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed. [ABSTRACT FROM AUTHOR]