PCSK9 as a New Player in Cancer: New Opportunity or Red Herring?
| Autor: | Francesco Dentali, Alessandra Vecchié, Francesco Grossi, Massimiliano Ruscica, Aldo Bonaventura |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
medicine.medical_treatment PCSK9 Liver Neoplasms Organic Chemistry Cancer Cholesterol LDL Immunotherapy Biology Proprotein convertase medicine.disease Biochemistry Liver regeneration Metastasis Receptors LDL Drug Discovery medicine Cancer research Animals Humans Molecular Medicine Kexin Cytotoxic T cell Proprotein Convertase 9 |
| Zdroj: | Current Medicinal Chemistry. 29:960-969 |
| ISSN: | 0929-8673 |
| DOI: | 10.2174/0929867328666211115122324 |
| Popis: | Initially described as a factor involved in liver regeneration and neuronal differentiation, proprotein convertase subtilisin/kexin type 9 (PCSK9) has become one of the key regulators of low-density lipoprotein cholesterol. Beside that, a number of studies have suggested PCSK9 may play a role in cancer biology. This is particularly true for gastroenteric (gastric and liver cancers) and lung cancers, where higher PCSK9 levels were associated with the increased ability of the tumor to develop and give metastasis as well as with reduced overall survival. Accordingly, monoclonal antibodies blocking PCSK9 were recently shown to synergize with immunotherapy in different types of cancers to achieve tumor growth suppression through an increased intratumoral infiltration of cytotoxic T cells. Anti-PCSK9 vaccines have been tested in animal models with encouraging results only in colon carcinoma. As most of this evidence is based on pre-clinical studies, this has led to some controversies and inconsistencies, thus suggesting that additional research is needed to clarify the topic. Finally, modulation of intracellular PCSK9 levels by silencing RNA (siRNA) may help understand the physiological and pathological mechanisms of PCSK9. |
| Databáze: | OpenAIRE |
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