PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology

Author:

Quagliariello Vincenzo1,Bisceglia Irma2,Berretta Massimiliano3ORCID,Iovine Martina1ORCID,Canale Maria Laura4,Maurea Carlo5,Giordano Vienna1,Paccone Andrea1,Inno Alessandro6ORCID,Maurea Nicola1ORCID

Affiliation:

1. Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy

2. Servizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy

3. Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy

4. U.O.C. Cardiology Department, Ospedale Versilia, Lido di Camaiore (LU), 55049 Camaiore, Italy

5. Department of Neurology, University of Salerno, 84084 Fisciano, Italy

6. Medical Oncology Department, IRCCS Ospedale Sacro Cuore Don Calabria, 37024 Negrar di Valpolicella, Italy

Abstract

Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions.

Funder

Italian Ministry of Health Ricerca Corrente funds

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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