T delivered at low dose rates. Th us
can define efficient MMR-cells resistant to chemotherapy and radiotherapy. Gegenw Ships to the use of iododeoxyuridine and other agents that preferentially accumulate in cells radiosensitizing defi cient MMR end under consideration MK-2206 as a means for the selective therapy resistant target cells. To the therapeutic ratio Maximize ratio, computational models to many experimental data are used to predict the optimal dose and IUDR IR. Moreover, knowledge of the mechanisms of resistance to chemotherapeutic agents resembled erm Specifically c drug selection guide. PARP inhibition, the base excision repair polymerase and synthetic lethality t Poly is the typical member of the PARP superfamily. Abundant nuclear protein, PARP is involved in a variety of cellular Ren processes of apoptosis infl ammation particular BER.
PARP tab containing zinc Fi nger motifs to recognize and bind to allow points of Sch At the einzelstr-Dependent DNA. Using NAD as substrate PARP catalyzes the addition of ADP-ribose polymer cha Ing side to himself, DNA ligase III, eff, DNA polymerase, XRCC and other components in the repair, and the recruitment and regulation ectors BER. Presence of PARP has been shown that the BER for effi cient operation. A plurality of molecules, most of which were nicotinamide NAD mimic part designed to inhibit the activity of PARP, BER prevents thus more efficient. Thesis agents have shown promising potential eff as a monotherapy in patients with tumors defi cient RH and potentiation ects traditional cytotoxic agents, including normal chemotherapy and radiotherapy.
Into two groups ver Ffentlichte the fi nd cient than BRCAdefi cells are sensitive to agents that inhibit PARP. E is the discovery generated intense interest, in part because of the potentially large therapeutic s exists in a situation in which the synthetic lethality present t. Synthetic lethality t occurs when two L versions T individually Dliche t Harmful if they combined. In this particular case, the human resources challenge BRCA mutant cells coefficients strongly dependent Ngig of other pathways of DNA repair, including normal BER, prevent the development of the CBD to its Unf Compensate ability to help repair DSB in a way, without any errors. If PARP is inhibited and thus BER that unrepaired single strand After all, lead to the collapse of the replication fork and CBD, lead immersing the cell machinery repair s and cell death.
Th e non tumor cells are better able to tolerate PARP inhibition because their HR machinery is intact. Synthetic lethality t represents a new strategy for the development of anti-cancer drugs. Chemotherapeutic herk Mmlichen therapeutics are relatively non-selective, often tion intended rapidly dividing cells, which include both the tumor and some normal cells. Designed using a synthetic lethality t approach k Can screening programs to identify more target genes are there. When mutated or inhibited, resulting in the death of cancer cells, the changes already zus USEFUL In the genes diff erent Normal cells should be spared because it is a combination of drug-induced to adversely Chtigung related to cancer, the t Harmful is is. DNA repair M Ngel, Epigen