Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model

NEN patients often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi) such as RAD001 (everolimus) has been shown to inhibit tumor progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of tumor cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppress autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy. In the current study we aim to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model, and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. We present here that CQ alone and in combination with RAD001 significantly decreased tumor volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and tumor cell growth, along with accumulation of autophagosomes and increased apoptosis. Therefore we concluded that CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on tumor progression in patients with NENs, mainly in those treated with mTORi, are warranted.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2H9Zld3