Personalized Systemic Therapies in Hereditary Cancer Syndromes

Luciana Mastrodomenico; Claudia Piombino; Beatrice Riccò; Elena Barbieri; Marta Venturelli; Federico Piacentini; Massimo Dominici; Laura Cortesi; Angela Toss

doi:10.3390/genes14030684

Personalized Systemic Therapies in Hereditary Cancer Syndromes

Genes (Basel). 2023 Mar 9;14(3):684. doi: 10.3390/genes14030684.

Authors

Affiliations

¹ Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, Italy.
² Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Abstract

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades.

Keywords: BRCA; MMR/MSI; PALB2; RET; VHL; hereditary cancer syndromes; personalized therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms, Hereditary Nonpolyposis* / drug therapy
Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
Germ-Line Mutation
Humans
Neoplastic Syndromes, Hereditary* / drug therapy
Neoplastic Syndromes, Hereditary* / genetics
Poly(ADP-ribose) Polymerase Inhibitors
Thyroid Neoplasms*

Substances

Poly(ADP-ribose) Polymerase Inhibitors

Grants and funding

Ricerca Finalizzata Giovane Ricercatore 2018 with the project GR-2018-12367239 (A.T.); Programma di ricerca sanitaria finalizzata Regione Emilia-Romagna (Fin-RER) (A.T.); Dipartimenti Eccellenti Fundings (Miur 2017) (M.D.).