Mechanisms
A review positions CETP alongside PCSK9 and ANGPTL3 as emerging lipid-regulatory targets in cancer, though CETP-specific oncology research remains scarce (Biomolecules 2026)
Original title: Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology
This narrative review examines dysregulated lipid metabolism as a contributor to tumor development and progression, evaluating PCSK9, ANGPTL3, and CETP as potential diagnostic biomarkers and therapeutic targets in oncology given their roles in cholesterol homeostasis, oncogenic signaling, and immune modulation within the tumor microenvironment. Most available evidence comes from preclinical and epidemiological studies, with PCSK9 by far the most extensively investigated of the three, while findings are often contradictory and strongly dependent on tumor type, disease stage, and biological context, currently precluding clinical use of any of these molecules as reliable biomarkers. Emerging preclinical evidence suggests modulating these glycoproteins, including CETP, may enhance chemotherapy, targeted therapy, and immunotherapy efficacy. The review notes that clinical research on PCSK9 inhibition in oncology is ongoing, whereas comparable clinical studies for ANGPTL3 and CETP remain scarce, calling for further mechanistic and translational investigation of the specific role of CETP in cancer biology.
Original abstract
Cancer remains a major global health challenge, with persistent limitations in early diagnosis, metastatic disease control, and the achievement of durable therapeutic responses with acceptable toxicity. These challenges highlight the need for more precise biomarkers and more effective therapeutic strategies. Increasing evidence implicates dysregulated lipid metabolism as a central contributor to tumor development and progression. In recent years, proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), and cholesteryl ester transfer protein (CETP) have gained particular attention due to their roles in cholesterol homeostasis, oncogenic signaling, and immune modulation within the tumor microenvironment (TME). This narrative review evaluates the potential of these lipid-regulatory mediators as diagnostic biomarkers and therapeutic targets in oncology. The majority of available evidence derives from preclinical and epidemiological studies, with PCSK9 representing the most extensively investigated target. Findings are sometimes contradictory and strongly influenced by tumor type, disease stage, and biological context, which currently precludes the clinical applicability of these molecules as reliable biomarkers. Similar limitations apply to their translational potential as actionable therapeutic targets. Nevertheless, emerging preclinical evidence suggests that modulation of these glycoproteins may enhance the efficacy of chemotherapy, targeted therapies, and immunotherapy, including nanomedicine-based approaches. Of note, clinical research investigating the role of PCSK9 inhibition in oncology is currently ongoing, whereas comparable studies focusing on ANGPTL3 and CETP remain scarce. Overall, further mechanistic, translational, and prospective clinical investigations are warranted to elucidate the involvement of these lipid-regulatory proteins in cancer biology and to define their potential integration into future oncologic diagnostic and therapeutic strategies.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.