Key result
PCSK9, ANGPTL3, and CETP show preclinical oncology potential but contradictory evidence precludes immediate clinical use.
Why the study?
Persistent limitations in cancer diagnosis and durable treatment, alongside growing evidence of dysregulated lipid metabolism in tumor progression, prompted evaluation of lipid-regulatory mediators as biomarkers and therapeutic targets.
While lipid-regulatory proteins like PCSK9, ANGPTL3, and CETP show preclinical promise as therapeutic targets in oncology, their clinical applicability remains limited by contradictory findings.
Should not alter oncology practice; leaves open whether PCSK9, ANGPTL3, or CETP inhibition improves cancer outcomes.
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.
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Kounatidis et al. (2026) conducted a review in Cancer. PCSK9, ANGPTL3, and CETP was evaluated. PCSK9, ANGPTL3, and CETP show potential as therapeutic targets in oncology, though current evidence is largely preclinical and contradictory, precluding immediate clinical application.
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