Download Old and new drugs for hereditary cancers Evgeny N. Imyanitov N.N.

Old and new drugs for hereditary cancers
Evgeny N. Imyanitov
N.N. Petrov Institute of Oncology, St.-Petersburg, Russia
There is an impressive progress in the development of specific treatments for hereditary
cancers. The most common type of familial cancer syndrome, BRCA1/2-related breast/ovarian
cancer (BC/OC), is characterized by a pronounced deficiency in the DNA double-strand break repair
by homologous recombination. This property causes high sensitivity of hereditary BC/OC to some
common drugs, such as cisplatin, mitomycin C, anthracyclines, etc. PARP-inhibitors represent the
first example of targeted therapy, which was specifically developed to treat tumors arising in germline mutation carriers. Some case reports and case series suggest potential utility of high-dose
chemotherapy for the management of BRCA1/2-driven malignancies. Exceptionally high plasticity
of BRCA1/2-related cancers significantly compromises therapeutic interventions resulting in a rapid
emergence of resistant clones. MSI-H colorectal tumors, including those arising in the context of
HNPCC syndrome, are highly antigenic and therefore can be managed by immune checkpoint
inhibitors. There are some other examples of targeted drugs, which are used for the treatment of
patients with orphan cancer syndromes. Turnaround time for genetic testing is a critical factor
affecting treatment decisions for the patients with hereditary cancers.