# Targeting Tumorigenic Coactivators in the PI3K/AKT Signaling Pathway: A Novel Approach for Cancer Treatment

## TL;DR

This paper reviews how targeting specific coactivators in the PI3K/AKT pathway could offer new cancer treatments by overcoming resistance and pathway overactivation.

## Contribution

The paper provides a novel synthesis of four tumorigenic coactivators and their roles in PI3K/AKT signaling for targeted cancer therapy.

## Key findings

- Each coactivator contributes to PI3K/AKT hyperactivation through distinct mechanisms.
- Therapeutic strategies like gene silencing and small-molecule inhibitors show promise but face challenges.
- The study highlights the convergent impact of multiple coactivators on cancer progression.

## Abstract

This study aims to explore the persistent activation of the PI3K/AKT signaling pathway in various cancers, with a focus on upstream coactivators that drive tumor growth and contribute to therapeutic resistance.

An integrated overview of four disparate tumorigenic coactivators of PI3K/AKT signaling, namely, TMEPAI (a transmembrane adaptor protein), SALL4 (a zinc‐finger transcription factor), TCL1B (an oncoprotein coactivator), and TGF‐β (a cytokine ligand) was identified and analyzed through a comprehensive literature review. Their mechanistic insights, signaling interactions, and therapeutic opportunities were also summarized.

The study outcomes demonstrate that each of these coactivators contributes to PI3K/AKT pathway hyperactivation and cancer progression through distinct mechanisms, such as the downregulation of negative regulators or direct enhancement of AKT activation. Emerging therapeutic approaches targeting these coactivators through gene silencing, small‐molecule inhibitors, and peptide‐based interventions were also outlined, along with associated challenges such as drug specificity, toxicity, and resistance.

By synthesizing evidence across these diverse molecules, this review highlights the convergent impact of multiple molecular classes on the PI3K/AKT pathway and outlines future perspectives for leveraging these insights in targeted cancer therapies.