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[PDF] Top 20 Synthetic lethal therapies for cancer: what's next after PARP inhibitors?

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Synthetic lethal therapies for cancer: what's next after PARP inhibitors?

Synthetic lethal therapies for cancer: what's next after PARP inhibitors?

... robust synthetic lethal effects ...of synthetic lethal effects is critical if effective treatments are to be developed but is still largely determined by empirical means ...robust ... See full document

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<p>PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives</p>

<p>PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives</p>

... endometrial cancer (EC) has a dismal prog- nosis due to poor response rates to conventional ...of cancer genetics and molecular biology has led to the devel- opment of targeted therapies, such as ... See full document

13

PARP inhibitors: Synthetic lethality in the clinic.

PARP inhibitors: Synthetic lethality in the clinic.

... CHEK1/2 inhibitors) has gained some traction of late, being bolstered by the recent development of drug- like WEE1 and ATR inhibitors that now make this a testable hypothesis in clinical trials ...targeting ... See full document

23

Advances and perspectives of PARP inhibitors

Advances and perspectives of PARP inhibitors

... on synthetic lethality theory, simultaneously blocking SSB repair and HR repair pathways could severely inhibit cell survival ...that PARP inhibi- tor (PARPi) could effectively kill BRCA1/2 mutated tumor ... See full document

12

PARP inhibitors in the management of breast cancer: current data and future prospects

PARP inhibitors in the management of breast cancer: current data and future prospects

... Tutt et al. [34] reported efficacy of olaparib as mono- therapy in 54 patients with advanced breast cancer and germline BRCA1/2 mutations. At the maximum tolerated olaparib dose of 400 mg bid, a 41 % objective ... See full document

16

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

... mutated cancer in just a decade ago, synthetic lethal approaches induced by Poly-(ADP-ribose)-polymerase (PARP) inhibitors (PARPi) have given renewed enthusiasm to developing anticancer ... See full document

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Comparative antiproliferative effects of iniparib and olaparib on a panel of triple negative and non triple negative breast cancer cell lines

Comparative antiproliferative effects of iniparib and olaparib on a panel of triple negative and non triple negative breast cancer cell lines

... reported that overexpression of miR-182 in the breast cancer cell line, MDA-MB-231 suppressed expression of BRCA1 and con- ferred sensitivity to two different PARP inhibitors. Conversely, ... See full document

9

Reverse the Resistance to PARP Inhibitors

Reverse the Resistance to PARP Inhibitors

... by PARP enzymes. Many clinical trials show that PARP inhibitors are promising in treatment of ...reducing inhibitors’ affinity for PARP1, restoring HR repair pathway, and suppressing ... See full document

11

A decade of clinical development of PARP inhibitors in perspective.

A decade of clinical development of PARP inhibitors in perspective.

... for cancer treatment as radio- and chemo-sensitizing drugs, but the aforementioned preclinical observations supported the development of PARPi as single agents for the treatment of BRCA1/2-defective ...with ... See full document

11

Resistance relationships between platinum and parp inhibitors in ovarian cancer

Resistance relationships between platinum and parp inhibitors in ovarian cancer

... additional reversion mutation (UPN-251) and (PEO1), also suggesting that there is a selective pressure against BRCA1/2 mutations in culture. • This effect has been observed in drug resistant cell lines, as well as in ... See full document

32

CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer

CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer

... bladder cancer cell system, we observed that the pharmacological inhibition of the USP7 deubiquitinase enhanced CCDC6 degradation, and by altering the DNA repair mechanisms mediated by homologous recombination, ... See full document

14

Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy

Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy

... Ovarian cancer is the leading cause of death in women with gynecological malignancy ...ovarian cancer treated with conventional therapy stimulated the search for new strategies to improve therapeutic ... See full document

8

LKB1 is a DNA damage response protein that regulates cellular sensitivity to PARP inhibitors

LKB1 is a DNA damage response protein that regulates cellular sensitivity to PARP inhibitors

... of PARP leads to the accumulation of SSBs, which are subsequently converted into DSBs at replication ...to PARP inhibitors ...lung cancer cell line H358, and three LKB1 deficient lung ... See full document

13

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

... 9]. PARP inhibition (PARPi) produces cell death via synthetic lethality in cancers with genetic predispositions for impaired DNA repair or impaired transcription, such as BRCA1 mutants [1, 10, ...breaks ... See full document

10

DNA repair in cancer: emerging targets for personalized therapy

DNA repair in cancer: emerging targets for personalized therapy

... to cancer. On the other hand, impaired DNA repair capacity in cancer cells may influence a favorable response to che- motherapy and ...repair inhibitors in combination with chemotherapy or ... See full document

16

Advances in using PARP inhibitors to treat cancer

Advances in using PARP inhibitors to treat cancer

... of PARP enzymatic activity in patient speci- ...of PARP inhibitors changes two parameters, each of which could be used as a phar- macodynamic endpoint: decreased PARP1/2-specific activity and ... See full document

5

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.

... ADP-ribosylation inhibitors are already in clinical development/use, given the essential role of ubiquitylation and de- ubiquitylation in the DDR, modulating DNA repair through the use of specific ... See full document

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An update on PARP inhibitors for the treatment of cancer

An update on PARP inhibitors for the treatment of cancer

... peritoneal cancer [NCT01012817]) and veliparib with met- ronomic cyclophosphamide (in refractory gynecological cancers, TNBC, and low-grade non-Hodgkin lymphoma [NCT01306032]) are currently ... See full document

10

Update on Poly ADP ribose polymerase inhibition for ovarian cancer treatment

Update on Poly ADP ribose polymerase inhibition for ovarian cancer treatment

... ovarian cancer; PARP: Poly(ADP-ribose) polymerase; PARPi: PARP inhibitors; HR: homologous recombination; HRD: homologous recombination deficiency; BRCA: breast related cancer antigens; ... See full document

18

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer

... Generation of tumour xenografts. All experiments were carried out in com- pliance with the UK Animals (Scienti fi cs Procedures) Act 1986 under a Project Licence and with the approval of the Cancer Research UK ... See full document

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