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Open AccessJournal ArticleDOI

Targeting PI3K in cancer: mechanisms and advances in clinical trials

TLDR
A critical review is performed to summarize the role of the PI3K pathway in tumor development, recentPI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3k inhibition.
Abstract
Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling is one of the most important intracellular pathways, which can be considered as a master regulator for cancer. Enormous efforts have been dedicated to the development of drugs targeting PI3K signaling, many of which are currently employed in clinical trials evaluation, and it is becoming increasingly clear that PI3K inhibitors are effective in inhibiting tumor progression. PI3K inhibitors are subdivided into dual PI3K/mTOR inhibitors, pan-PI3K inhibitors and isoform-specific inhibitors. In this review, we performed a critical review to summarize the role of the PI3K pathway in tumor development, recent PI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3K inhibition.

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Therapeutic Targeting of the Tumor Microenvironment

TL;DR: A comprehensive analysis of the current therapies targeting the tumor microenvironment (TME) is provided in this paper, combining a discussion of the underlying basic biology with clinical evaluation of different therapeutic approaches, and highlighting the challenges and future perspectives.
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The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling.

TL;DR: This review outlines the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discusses new mechanistic insights into the interplay between the PI3k-AKt- mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance.
Journal ArticleDOI

Trends in kinase drug discovery: targets, indications and inhibitor design.

TL;DR: In this paper, the authors analyzed the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors and their expanding range of indications.
Journal ArticleDOI

Clear cell renal cell carcinoma ontogeny and mechanisms of lethality.

TL;DR: This Review summarizes common genomic and chromosomal copy number abnormalities in ccRCC, providing a mechanistic framework with which to organize these features into initiating events, drivers of progression and factors that confer lethality.
Journal ArticleDOI

Sex differences in cancer mechanisms.

TL;DR: The goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research.
References
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Journal ArticleDOI

AKT/PKB signaling: navigating downstream.

TL;DR: Those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration are discussed.
Journal ArticleDOI

The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

TL;DR: In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
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