Hereditary cancer syndromes

utilizing DNA repair deficiency as therapeutic target

Gaurav Goyal, Tiffany Fan, Peter T. Silberstein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on the utility of the defects in DNA repair as targets for cancer therapy in these syndromes. Novel therapies like poly (ADP-ribose) polymerase (PARP) inhibitors are one of such example where the induction of double stranded breaks in DNA leads to tumoricidal effect in patients with homologous DNA repair deficiency. Interestingly, patients with DNA repair deficiencies tend to have a more favorable prognosis than sporadic malignancies. In microsatellite high colorectal cancer patients, this has been attributed to increased recruitment of CD8+ T lymphocytes in tumor microenvironment. However, these tumors are able to limit the host immune response by activation of immune checkpoints that seem like attractive targets of therapy in the future.

Original languageEnglish
Pages (from-to)359-366
Number of pages8
JournalFamilial Cancer
Volume15
Issue number3
DOIs
StatePublished - Jul 1 2016

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Hereditary Neoplastic Syndromes
DNA Repair-Deficiency Disorders
Neoplasms
Breast Neoplasms
Colorectal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Therapeutics
Tumor Microenvironment
Double-Stranded DNA Breaks
Neoplasm Genes
DNA
Platinum
DNA Repair
Microsatellite Repeats
Ovarian Neoplasms
Carcinogenesis
T-Lymphocytes
Mutation

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)

Cite this

Hereditary cancer syndromes : utilizing DNA repair deficiency as therapeutic target. / Goyal, Gaurav; Fan, Tiffany; Silberstein, Peter T.

In: Familial Cancer, Vol. 15, No. 3, 01.07.2016, p. 359-366.

Research output: Contribution to journalArticle

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