Hereditary cancer syndromes

Table 2 Cytotoxic and targeted therapy for tumors arising in carriers of cancer-predisposing alleles

Tumor type	Target	Drugs	Ref.
BRCA1/2-driven carcinomas and their phenocopies	BRCA1/2 inactivation resulting in the deficiency of DNA repair by homologous recombination	Platinum derivatives, Mitomycin C, Bifunctional alkylating agents, PARPi	[190-193,195]
Hypermutated cancers (Lynch syndrome associated microsatellite unstable tumors; POLD1/POLE-deficient cancers; MUTYH-associated colorectal carcinomas; tumors in patients with CMMRD syndrome)	High tumor mutation burden resulting in excessive number of neoantigens	Immune checkpoint inhibitors	[199-206]
RET-associated malignancies	RET tyrosine kinase	RET inhibitors	[207-209]
Neurofibromatosis, type 1	Upregulation of RAS/RAF/MEK pathway due to NF1 inactivation	MEK inhibitors	[210,211]
Basal cell carcinomas in patients with Gorlin syndrome	Hedgehog pathway	SMO inhibitors	[213]
Tumors arising in patients with tuberous sclerosis	mTOR pathway	mTOR inhibitors	[214,215]
Renal cell carcinomas associated with von Hippel-Lindau syndrome	Up-regulation of HIF-2α due to VHL gene inactivation	HIF-2α inhibitors	[216]

HIF-2α: Hypoxia inducible factor-2α; PARPi: Poly (ADP-ribose) polymerase inhibitors; CMMRD: Constitutional mismatch repair deficiency syndrome; MEK: Mitogen-activated protein kinase; SMO: Smoothened; mTOR: Mechanistic target of rapamycin; VHL: von Hippel-Lindau.