Disruption of the Fanconi anemia/BRCA pathway in sporadic cancer.

An increasing number of studies provide evidences linking disruption of Fanconi anemia/BRCA cascade with sporadic cancers. Given that this pathway plays essential roles in response to the DNA interstrand cross-links, these cancers are expected to be chemosensitive to cross-link based therapy. In the present mini-review we expand the spectrum of possibilities for FA/BRCA disruption and review some works describing functional upstream and downstream events linking disruption of the FA/BRCA pathway to sporadic cancer. This may involve but not limited to epigenetic silencing of the FA-core complex or BRCA1/2, mutations of one or several FA-BRCA genes or modification of encoded products. All this may serve as a platform for occurrence, development and treatment of sporadic cancers and therefore deserves to be in the focus of new research directions.