MedComm (2020). 2026 Mar 2;7(3):e70656. doi: 10.1002/mco2.70656. eCollection 2026 Mar.

ABSTRACT

Chemotherapy is the mainstay in the treatment of advanced gastric cancer (GC); yet, GC showed diverse responses to first-line chemotherapy regimens and the underlying molecular basis is still not clear. Here, we established a system that combined organoid-based chemotherapy regimen screening and transcriptome-based evaluation to identify underlying molecular signatures of different responses to chemotherapy. We generated 19 GC patient-derived organoids (PDOs) from surgically resected specimens with corresponding histological characteristics of parent tumors and tested all of the five most commonly used first-line chemotherapy regimens. Based on the treatment responses, PDOs were classified into double-sensitive, single-sensitive, and not-sensitive groups. PDOs that responded well to chemotherapy presented high expression levels of the P53 pathway genes and low expression levels of cell proliferative activity genes. Furthermore, the chemotherapy-based tumor classification of GC was established. The GC tumor classification was verified by multi-omics features from the TCGA dataset and public drug response datasets. In conclusion, this study systematically evaluated clinical chemotherapy regimens for GC and identified chemotherapy response-associated molecular signatures based on human GC organoids, which are beneficial to the precise treatments of GC.

PMID:41782964 | PMC:PMC12954136 | DOI:10.1002/mco2.70656

Int J Surg. 2025 Jul 15. doi: 10.1097/JS9.0000000000003049. Online ahead of print.

ABSTRACT

Fatty acid-binding proteins (FABPs) are intracellular lipid chaperones with molecular weights of approximately 14-15 kDa. By binding and transporting fatty acids and lipid-related molecules, FABPs precisely regulate metabolic pathways, signal transduction, and gene expression, playing a central role in cancer initiation and progression. The 11 identified subtypes (FABP1-FABP12; FABP11 is identical to FABP3) exhibit tissue-specific expression and influence tumor progression through metabolic reprogramming, immune microenvironment modulation, and therapy resistance. Metabolically, FABPs enhance fatty acid uptake, β-oxidation, and synthesis, meeting the high proliferative demands of tumors. In immune regulation, FABP4+ macrophages secrete IL-6 to suppress T cell activity, while FABP6 downregulates MHC-I molecule expression to reduce CD8+ T cell infiltration, fostering an immunosuppressive microenvironment. Regarding therapy resistance, FABP4 enhances mitochondrial β-oxidation to reduce apoptosis in ovarian cancer, and FABP5 promotes chemoresistance in HCC via the HIF-1α pathway. Functional heterogeneity exists among subtypes: FABP7 drives glioblastoma stem cell migration via RXRα signaling, while FABP5 exhibits context-dependent roles, promoting HCC progression but suppressing colorectal cancer (CRC) through mTOR-mediated autophagy. Clinically, FABPs serve as diagnostic biomarkers and therapeutic targets. However, challenges such as insufficient target specificity, cross-cancer heterogeneity, and normal tissue toxicity remain. Future studies should integrate multi-omics and single-cell technologies to elucidate cell-specific mechanisms and develop precise combination therapies for clinical translation.

PMID:40717587 | DOI:10.1097/JS9.0000000000003049