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Phytochemicals and Nanoparticles in the Modulation of PI3K/ Akt/ mTOR Kinases and Its Implications in the Development and Progression of Gastrointestinal Cancers: A Review of Preclinical and Clinical Evidence.

BACKGROUND
Gastrointestinal cancer are the major form of cancer in developing countries which comprises gastric cancer (GC), hepatic cancer (HCC), colorectal cancers (CRC) etc; they account for a large number of cancer-related deaths globally. Gastrointestinal cancers generally have a multifactorial origin, where both genetic and dietary factors play prominent roles. PI3K/Akt signaling is the prime signaling pathway associated with Phosphoinositide-3 kinase/protein kinase B signaling pathway.


OBJECTIVE
The present review aims to summarize the role of PI3K/Akt signaling pathway on the different events of gastrointestinal cancers such as proliferation, survival, metastasis, angiogenesis, drug resistance and stem cell properties.


METHODS
Literature collection has been done using the appropriate keywords from PubMed/Medline, Scopus, Web of science, or Eurekaselect. The details of individual types of cancers were selected by giving respective keywords.


RESULTS
PI3K signaling pathway is important in various gastrointestinal carcinogenesis and progression events; the pathway is involved in proliferation, survival, metastasis, and drug resistance. Several natural phytochemicals and their derivatives have been shown to inhibit PI3K signaling and its downstream regulatory elements, subsequently resulting in an anticancer and anti-metastatic activity. Although numerous preclinical evidences are available, conclusive clinical reports are lacking on the anticancer aspects of PI3K inhibitors in gastric cancer.


CONCLUSION
Phytochemicals are promising drug candidates by targeting PI3K/mTOR pathway in various gastrointestinal cancer treatments. However, there is a need for extensive clinical studies to ascertain the commercial value as anticancer therapeutic compounds against cancers of the stomach, liver, and intestine.