ACSL5 (Acyl-CoA Synthetase Long Chain Family Member 5)

The ACSL family serves as a key regulatory node integrating lipid metabolism, ferroptosis, and tumor immunity. Its isoform-specific mechanisms and context-dependent characteristics highlight its potential as a precise therapeutic target. Future research should focus on optimizing isoform-selective inhibitors, clarifying their synergistic effects with existing therapies (e.g., immune checkpoint inhibitors, radiotherapy), and validating their translational efficacy through clinical trials to advance the development of innovative cancer treatment strategies.

In patient cohorts with HCC, those with lower AOX1 expression exhibited a more pronounced therapeutic response to deuterated sorafenib. Overall, the present study elucidates the mechanism by which deuterated TKIs reverse TKI resistance by promoting ferroptosis and suggests that AOX1 could serve as a biomarker to guide clinical decision-making for deuterated TKI treatment in HCC.

This deep learning model demonstrated excellent performance in multi-omics subtype predictions. In, conclusion, this study systematically elucidates the molecular heterogeneity of LUAD through a multi-omics integration strategy, establishes a clinically relevant molecular classification system, and provides a theoretical foundation for developing personalized treatment plans for LUAD.

Limiting PA intake or targeting the ACSL5/COX2/EP4 axis enhanced paclitaxel efficacy in a breast cancer mouse model. Collectively, these findings highlight the critical role of PA and ACSL5/COX2/EP4 signaling in lung metastasis, which can act as promising targets for enhancing the efficacy of chemotherapy in BC patients with lung metastasis.

Notably, JAB1 inhibition reverses chemotherapy resistance associated with CUL4B overexpression. These findings underscore the pivotal role of JAB1 in regulating breast cancer progression and indicate that JAB1 inhibitors could serve as promising therapeutics for patients with elevated CUL4B expression.

Nonetheless, these metabolic increases also generate reactive oxygen species (ROS), inducing DNA damage and significantly enhancing colorectal cancer cell sensitivity to oxaliplatin. The latter provides an explanation as to why colorectal tumors with high ACSL5 expression display preferentially improved patient outcomes from chemotherapy. Collectively, the findings reveal a new pathway for non-genetic chemotherapy resistance mechanisms, deepen the understanding of metabolic reprogramming in tumor cells, and offer potential therapeutic targets for future treatment strategies.

The present review seeks to fill this gap by summarizing recent advances in understanding the roles of the ACSL family across diverse diseases, with a focus on emerging therapeutic strategies that target these enzymes. This work provides critical insights that may inform future preclinical and clinical investigations of the ACSL family.

These results indicate that OCIAD2 is a potential prognostic biomarker and therapeutic target for PC patients.

Finally, SOX2 expression correlates negatively with ACSL5 and positively with histone acetylation in clinical esophageal squamous tumors. Altogether, our study uncovers a role of SOX2 in reprogramming lipid metabolism and driving histone hyperacetylation and super-enhancer function, providing mechanistic insights of SOX2 acting as a potent oncodriver.

Lastly, single-cell RNA-sequencing revealed elevated ACSL4 expression in immune cells in a murine MASH-HCC model, suggesting a role of ACSL4 in shaping the tumor immune microenvironment. Overall, this report offers new insights into lipid metabolic landscape and ferroptosis sensitivity for novel MASH-HCC treatments.

These results provide valuable insights into potential biomarkers and therapeutic targets for BLCA treatment. The CHMP6 protein promotes BLCA cell survival and invasive migration through modulation of the cell cycle.

In summary, our study revealed that ACSL5-mediated lipid oxidation increases the acetyl-CoA content, promotes cellular senescence, and inhibits the proliferation of BC. The activation of ACSL5-mediated lipid oxidation to regulate cellular senescence may provide an innovative direction for BC therapy.