Abstract 7374: Body size and composition in relation to PI3K/AKT/mTOR signaling: insights into cancer risk and outcomes - a systematic review
Authors: Rand Lucine Akasheh, Cuthbert Mario Mahenge, Faiza Kalam, Anita Adib, Stephanie Schulte, Ting-Yuan David Cheng
Journal: Cancer Research (2025)

Abstract Objective: To synthesize evidence from studies investigating the relationship between body size and composition with PI3K/AKT/MTOR signaling in the context of cancer risk and outcomes. Methods: A systematic search of the literature was conducted in Web of Science, Embase, and Pubmed as of January 2019. The inclusion criteria entailed studies that reported any anthropometric measure of body size and/or composition; and any measure of gene, RNA, or protein expression in PI3K/AKT/MTOR signaling, or that directly or indirectly interacts with the pathway in tumors, precancerous lesions, adipose, or muscle tissue; and included people with cancer or precancerous lesions, cancer survivors, high-risk populations, or/and populations with average risk for studying cancer risk. Results: The search strategy resulted in 6258 studies, of which 1198 studies were excluded by deduplication. Titles and abstracts of the remaining 5087 studies were screened and 4471 studies were found irrelevant and therefore excluded, leaving 316 studies for full-text screening. Of these, 173 studies were excluded leaving 143 studies that met the inclusion criteria and were used in full-text extraction. The included studies focused on gastrointestinal cancers (n = 50: 35 colorectal, 2 upper GI, 3 gastric, 4 esophageal with 1 on Barrett cases, 5 pancreatic, and 1 hepatic); gynecological cancers (n = 34: 32 endometrial with 4 on normal endometrium of at-risk women, 1 cervical, 1 ovarian); breast cancer (n = 31: with 2 on normal breast tissue of at-risk women); male reproductive cancers (n = 7: 6 prostate, 1 Leydig cell); lung cancer (n = 6); thyroid cancer (n = 6); renal cancer (n = 2); skin cancer (n = 1); and cancer cachexia across cancer sites (n = 6). Body size and composition modulate many components of PI3K/AKT/MTOR pathway, in addition to upstream and downstream effectors. Numerous studies indicate that obesity modifies the relationship between molecules in the PI3K/AKT/MTOR pathway and cancer survival, while alterations in this pathway may also affect how body size and composition relate to cancer survival. However, inconsistency in findings was observed due to heterogeneity in study design, exposure variables, reported effect estimates, population characteristics, cancer and tumor features, and methods of outcome measurements. This heterogeneity precluded a meta-analysis. Instead, a qualitative synthesis was conducted to integrate key insights and trends. Conclusions: The review highlights the broad impact of obesity on cancer biomarkers and outcomes and emphasizes the need for standardized study design and consistent reporting in future research to facilitate meta-analyses and robust conclusions. Most studies relied solely on BMI as a measure of body size, revealing a substantial research gap in examining the relationship between body adiposity and muscularity with PI3K/AKT/mTOR signaling. Citation Format: Rand Lucine Akasheh, Cuthbert Mario Mahenge, Faiza Kalam, Anita Adib, Stephanie Schulte, Ting-Yuan David Cheng. Body size and composition in relation to PI3K/AKT/mTOR signaling: insights into cancer risk and outcomes - a systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7374.