Abstract A27: The relationship between aspirin and cancer via its inhibition of mTOR pathway
Authors: Karabulut Bulent , Ay Oyku 
Published: December 2020

Abstract
Aspirin, a nonsteroidal anti-inflammatory drug, has been used clinically as a painkiller, antipyretic or antiplatelet agent for more than 100 years. Several trials demonstrate that the nonsteroidal anti-inflammatory agent aspirin prevents NETs (neuroendocrine tumors), colorectal cancer (CRC), hepatocellular carcinoma (HCC), melanoma, glioma, bladder cancer, pancreatic cancer (PC), breast and prostate cancers and reduces cancer mortality, indicating a promising role of aspirin for cancer prevention. In literature, we can see that most of them are clinical studies. For more effective treatment we need to understand molecular mechanism. In this study, we reviewed the relationship between aspirin and mTOR pathway in types of cancer mentioned above, particularly CRC since it is better defined. The main question is: How can aspirin inhibit the cancer development by using mTOR pathway? The benefit-to-risk ratio must be defined in different cancer types as side effects. Mammalian target of rapamycin (mTOR) is highly expressed in the processes of multiple types of tumors. mTOR forms the catalytic core of 2 distinct complexes, mTORC1 and mTORC2. mTORC1 integrates growth factor and nutrient signals to influence protein synthesis, growth, autophagy, and ribosomal biogenesis. The role of mTORC2 is less well defined. Aspirin reduced the incidence and mortality of colorectal cancer by activating the adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK)/mTOR pathway and contributed to protection against the development of CRC. Aspirin inhibits mTORC1 signaling in an AMPK-independent manner. AMPK plays a major role in cellular energy hemostasis and leads to mTOR suppression. Some studies investigated the effects of aspirin on AMPK/mTOR signaling and showed that aspirin alone or the combination of aspirin and metformin activates AMPK and inhibits mTOR signaling in colorectal cancer cells. Furthermore, mutations in phosphatidylinositol 3-kinase (PI3K) signaling genes occur in 40% of CRCs and that pathway is important in regulating the cell cycle, although mTOR is a downstream effector of the PI3K/AKT pathway. In PC, NETs and CRC the PI3K/Akt/mTOR pathway is deregulated in the majority of tumors, and the activation of this pathway correlates significantly with a poor prognosis. A link between cancer and metabolism has been long suggested. Additionally, aspirin induced autophagy, a feature of mTOR inhibition. So mTOR exists in a phosphorylated form in normal conditions and suppresses autophagy. Much available evidence supports AMPK/mTOR signaling as a chemoprevention target. Some studies have suggested that aspirin is a promising agent for adjuvant therapy to increase survival. However, the mechanism of combination and its effects on patients require further prospective investigations. In conclusion, aspirin inhibits the cancer development and progression by using mTOR signaling pathway.
Note: This abstract was not presented at the conference.
Citation Format: Bulent Karabulut, Oyku Ay. The relationship between aspirin and cancer via its inhibition of mTOR pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A27.