The Slamon and Finn groups at UCLA have discovered that specific chromosomal gains can serve as biomarkers that predict a cancer patient response to treatments that use poly-ADP ribose polymerase (PARP) inhibitors.
Poly-ADP ribose polymerase (PARP) is an enzyme that plays a critical role in DNA repair. Since alterations or changes in DNA repair pathways have been implicated in the pathogenesis of human cancers, PARP inhibition has been put forward as a potential strategy to treat various cancers. Several small molecule inhibitors of PARP have been developed, and show growth inhibitory activity in a small number of human cancers. Specifically, the use of PARP inhibitors has been validated in cancers that lack specific DNA repair mechanisms either through inherited mutations and/or non-inherited silencing of specific genes, such as BRCA1 and BRCA2.
The biomarkers that are most frequently used to identify potential patients with cancers that would be responsive to PARP inhibition are inherited mutations in either the BRCA1 or BRCA2 gene. Therefore, those identified are typically breast or ovarian cancer patients. However, not all BRCA-mutated breast and ovarian cancers respond to PARP inhibition. Additionally, only a minority of patients with breast and ovarian cancer have inherited mutations in the BRCA genes. Therefore, a more robust biomarker for sensitivity to PARP inhibition would increase the patient population that successfully receives PARP inhibition treatment for cancer.
Researchers at UCLA have discovered specific chromosomal alterations that serve as biomarkers for cancer patient sensitivity to PARP inhibitors. Using over 300 cell lines that include over 15 different cancer types, they found that a genomic gain in chromosome 1q21 and/or chromosome 20q13.3 were robust biomarkers of sensitivity to this type of treatment. Their results showed a number of cancers other than breast and ovarian cancers that are sensitive to this type of treatment, including malignancies of the lung, bladder, stomach, colon, rectal, and liver, as well as cancers in the head and neck regions.
Easy to implement in the clinic:
The predictive potential of the two independent chromosomal biomarkers of sensitivity to PARP inhibitors has been validated in over 300 human cancer cell lines.
Future work includes validation of biomarkers in clinical human specimens.
|United States Of America||Published Application||2017-036995||12/28/2017||2013-716|
PARP inhibition, poly-ADP Ribose Polymerase, cancer biomarker, breast, ovarian, lung, bladder, stomach, colorectal, liver, head, neck