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http://www.ncbi.nlm.nih.gov/m/pubmed/22889437/?i=5&from=ovarian%20cancer
Wednesday, August 15, 2012
1 comment :
BRCA1 is a response element for DNA damage and part of FANC gene family (a genomic fidelity function).
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Dr. Robert A. Nagourney's lab (Rational Therapeutics) has observed good activity for the PARP inhibitors as single agents in BRCA1 positive ovarian patients. Work is ongoing with these BRCA1 positive patients. This seems to be an important class of new drugs for the treatment of BRCA1 mutant tumors.
Olaparib seems to have demonstrated, in a phase 2 clinical studies, significant response rates in patient with ovarian cancer associated with BRCA1 mutations, as reported at the 2010 ASCO trade show. Olaparib is a small molecule, potent oral poly (ADP-ribose) polymerase (PARP) inhibitor.
A favored mechanism for repair of double-strand breaks is homologous recombination, a BRCA1-dependent process in which the homologous sequence is used to precisely repair the break. A patient with an inherited BRCA1 mutation has normal BRCA function, owing to the one functional allele, but in the cancer this allele is usually inactivated, rendering the tumor cells selectively deficient in homologous recombination.
Poly (adenosine diphosphate-ribose) polymerases (PARPs) are important regulators of the base excision repair pathway, a DNA repair pathway that becomes vital to cells defective in homologous recombination. Therefore, in tumor cells lacking homologous recombination, pharmacological inhibition of PARP may lead to persistent double-strand breaks, inducing cell death (Farmer et al. 2005).
When copies of the BRCA1 genes are faulty, the cells rely on the alternative PARP pathway to repair damaged DNA, preventing cancer-causing mistakes being passed on to daughter cells. By also blocking PARP with drugs, cancer cells which have lost BRCA1 can no longer repair DNA damage at all, causing these cancer cells to die. Serous ovarian cancer patients may have DNA repair deficits that could make them sensitive to treatment with a PARP inhibitor.
I would imagine additional studies of the function of BRCA1 mutation is needed to more fully understand and treat this type of cancer.
]http://cancerfocus.org/forum/showthread.php?t=3384
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BRCA1 is a response element for DNA damage and part of FANC gene family (a genomic fidelity function).
ReplyDeleteDr. Robert A. Nagourney's lab (Rational Therapeutics) has observed good activity for the PARP inhibitors as single agents in BRCA1 positive ovarian patients. Work is ongoing with these BRCA1 positive patients. This seems to be an important class of new drugs for the treatment of BRCA1 mutant tumors.
Olaparib seems to have demonstrated, in a phase 2 clinical studies, significant response rates in patient with ovarian cancer associated with BRCA1 mutations, as reported at the 2010 ASCO trade show. Olaparib is a small molecule, potent oral poly (ADP-ribose) polymerase (PARP) inhibitor.
A favored mechanism for repair of double-strand breaks is homologous recombination, a BRCA1-dependent process in which the homologous sequence is used to precisely repair the break. A patient with an inherited BRCA1 mutation has normal BRCA function, owing to the one functional allele, but in the cancer this allele is usually inactivated, rendering the tumor cells selectively deficient in homologous recombination.
Poly (adenosine diphosphate-ribose) polymerases (PARPs) are important regulators of the base excision repair pathway, a DNA repair pathway that becomes vital to cells defective in homologous recombination. Therefore, in tumor cells lacking homologous recombination, pharmacological inhibition of PARP may lead to persistent double-strand breaks, inducing cell death (Farmer et al. 2005).
When copies of the BRCA1 genes are faulty, the cells rely on the alternative PARP pathway to repair damaged DNA, preventing cancer-causing mistakes being passed on to daughter cells. By also blocking PARP with drugs, cancer cells which have lost BRCA1 can no longer repair DNA damage at all, causing these cancer cells to die. Serous ovarian cancer patients may have DNA repair deficits that could make them sensitive to treatment with a PARP inhibitor.
I would imagine additional studies of the function of BRCA1 mutation is needed to more fully understand and treat this type of cancer.
]http://cancerfocus.org/forum/showthread.php?t=3384