BRCAness Ph Genotype as dysfunction of genes involved in webs of CR and DDR. BRCAness Ph Phenomena have been identified recently in a growing list of cancers, and we are in favor of attention to these genetic and epigenetic Ver Changes in a more comprehensive way erh Ht. Particularly, not only in BRCAness triple CYC202 Roscovitine negative breast cancer, but also in epithelial ovarian cancer and other cancers such as non-small cell lung cancer head and neck cancer, prostate cancer and Geb Rmutterhalskrebs. Ph Phenotypic characterization BRCAness is always a new and attractive strategy for the treatment of cancer patients with targeted therapies PARP inhibitors. Combination therapy with inhibitors of PARP PARP inhibitors may be used as radiosensitizers chemotherapy in combination with chemotherapeutic agents or radiation therapy, and as the platinum compounds, and methylating agent.
to date were PARP inhibitors as Olaparib, ABT 888, iniparib, mp 01367338, MK4827, CEP 9722, INO 1001 in combination with chemotherapy or radiotherapy in phase I or phase II clinical use WYE-354 in the treatment of triple negative breast cancer, metastatic melanoma, glioma, colon cancer. PARP inhibitors obtained Hen the antitumor activity of t of ionizing radiation and DNA beautiful ended ligands chemotherapeutic agent. There are several m Possible mechanisms that guide combination therapy After exposure to chemotherapeutic drugs, confinement can Lich PARP BER pathway is an essential element, activated k and k can the side effects of chemotherapy, which causes resistance to therapy to reverse . The combination of PARP inhibitors and chemotherapy verst Strengths k Can the toxic effects, particularly induce if the effect of the DNA strand breaks. Some active ingredients, for example, compounds of platinum and a compound of methylation in this category. For example, the Gro Part of the DNA-Sch Ending caused by temozolomide is repaired by BER.
Inhibition of PARP w Prevented during temozolomide treatment repair by BER in cancer cells and leads to tumor cell death. In a Phase II study in metastatic melanoma, the combination of PF 01367338 temozolomide was more myelosuppressive than the expected profile with a single agent and vorl INDICATIVE results have shown improved response rates and progression-free survival. PARP inhibitors can k Also function as sensitizers to improve the therapeutic sensitivity of chemoradiation and can resistance to treatment galv Gladly. This theory was best by a series of pr Clinical trials with different PARP inhibitors in tumor models CONFIRMS. A recent study showed that awareness of ionizing radiation and alkylating agent methyl methane sulfonate by Olaparib was improved in cells deficient in DSB repair. Awareness was dependent Ngig DNA replication and repair associated with failures-Sch Replication Artemis and ATM MEF cells. Another study showed that the combination of a PARP inhibitor and sulfonate methyl methanesulfonate