PI3K/Akt/mTOR Signaling Pathway in Blood Malignancies—New Therapeutic Possibilities

SIMPLE SUMMARY: The PI3K/Akt/mTOR pathway plays a crucial role in cancer, including leukemia. Abnormalities in this pathway drive carcinogenesis by inducing uncontrolled growth, increased survival, and treatment resistance. The abovementioned pathway is also disrupted in various types of leukemia, which makes it a potential therapeutic target for this disease. Current treatment approaches for leukemia are limited and fraught with numerous side effects. This review article aims to summarize recent research data on inhibitors of the PI3K/Akt/mTOR pathway. Inhibition of this pathway may potentially provide improved treatment outcomes for leukemia. ABSTRACT: Blood malignancies remain a therapeutic challenge despite the development of numerous treatment strategies. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway plays a central role in regulating many cellular functions, including cell cycle, proliferation, quiescence, and longevity. Therefore, dysregulation of this pathway is a characteristic feature of carcinogenesis. Increased activation of PI3K/Akt/mTOR signaling enhances proliferation, growth, and resistance to chemo- and immunotherapy in cancer cells. Overactivation of the pathway has been found in various types of cancer, including acute and chronic leukemia. Inhibitors of the PI3K/Akt/mTOR pathway have been used in leukemia treatment since 2014, and some of them have improved treatment outcomes in clinical trials. Recently, new inhibitors of PI3K/Akt/mTOR signaling have been developed and tested both in preclinical and clinical models. In this review, we outline the role of the PI3K/Akt/mTOR signaling pathway in blood malignancies’ cells and gather information on the inhibitors of this pathway that might provide a novel therapeutic opportunity against leukemia.