Recently, we discovered that a subset of TNBC significantly cant a new sub-type, low claudin what is important is because it is biologically different from BLBC and a number of properties are reminiscent of mammary stem cells. Zus Tzlich luminal A, luminal B, and H ER2 tumors are enriched in adorns TNBCs identified in various small proportions, underscores the complexity t of cation-based clinical classification. We investigated VX-745 the sensitivity of the treatment of various subtypes neoadjuvant anthracycline intrinsic / taxane-based chemotherapy with a large database of s PUBLIC train Accessible. In all patients and in TNBC basal like tumors were found associated with a gr Eren probability of a pathological completely Ndiges response Including the rest of the subtypes Lich lower claudine. Predict in multivariate models using logistic regression PCR, we found that the intrinsic molecular subtypes. Almost always the fi nal model, although the clinical variables and other genomic Pr Predictors are included It also analyzes show our that these tumors reach a PCR showed better chances of survival than those who do not independently Ngig of their molecular subtype, the eff gr much It in the sub-base, such as type, which is with previous fi ndings .
T This fascinating combination of residual disease after treatment and poor prognosis in basal and claudin and sw Chen tumors intratumoral heterogeneity Than an m Possible explanation insurance, Where strong and aggressive. BioMed Central Ltd. 2010 cell clones present in perhaps the pretreated tumor. WYE-354 Our analyzes vorl ufigen Using a combination of-Activated cell sorting uorescente and global gene expression in many pr Clinical models of breast cancer basallike including normal cell lines and xenografts from primary Suggest rtumoren the existence of at least two populations of cells in many models BLBC. Diff erent these cell populations can be tested for the activity T initiators of tumor cells, and further studies of these populations with changing treatment also run. Polymerase enzyme poly 1 is activated by a DNA-binding nuclear DNA strand breaks, and plays an r Signaling the major breakthroughs in single-stranded DNA in the repair.
In cancer cause many agents DNA Sch To that t their mechanism of cytotoxicity And repair of Sch The tumor is a cause of resistance. Moreover, in tumors, in which the double-strand breaks repair defective PARP inhibitors have potential activity t monotherapy. Sun PARP 1 was identifies as potential therapeutic targets for the treatment of cancer and PARP inhibitors in the clinic in combination with chemotherapy appeared as a unique DNA repair challenge cient tumors, and more recently, in combination with radiotherapy. Should be the PARP inhibitor fi rst of cancer patients in 2003 AG014699, a tricyclic indole, which is a potent inhibitor of PARP intravenous S. This phase I study was a criterion pharmacodynamic inhibition of PARP in PBMCs, demonstrating for the fi rst time reference to the mechanism of the class. Subsequently AZD2281 end. In clinical trials as monotherapy and demonstrated the proof of concept of synthetic lethality t in BRCA defective tumors in two small Phase II studies In the past seven years, 5 inhibitors are complementary Re inp Nge cancer clinical trials, either as monotherapy or in combination with various cytotoxic regiments in the pr Clinical development.