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Catalytic inhibition of KDM1A in Ewing sarcoma is insufficient as a therapeutic strategy.
(WILEY, 2019-09-01)
BACKGROUND: Ewing sarcoma and desmoplastic small round cell tumors (DSRCT) are rare and clinically aggressive sarcomas usually characterized by oncogenic fusion proteins involving EWS. Emerging studies of Ewing sarcoma ...
Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma.
(BMC, 2020-03-30)
BACKGROUND: Multiple myeloma (MM) remains incurable despite recent therapeutic advances. RAS mutations are frequently associated with relapsed/refractory disease. Efforts to target the mitogen-activated protein kinase ...
A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation.
(WILEY, 2018-12-01)
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors ...
Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval.
(FUTURE MEDICINE LTD, 2022-07-26)
Over the past 20 years, the management of gastrointestinal stromal tumors has acted as an important model in the advancement of molecularly targeted therapies for solid tumors. The success of imatinib has established it ...
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.
(NATURE PUBLISHING GROUP, 2016-12-13)
Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
Exploiting Synthetic Lethality and Network Biology to Overcome EGFR Inhibitor Resistance in Lung Cancer.
(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2017-06-16)
Despite the recent approval of third-generation therapies, overcoming resistance to epidermal growth factor receptor (EGFR) inhibitors remains a major challenge in non-small cell lung cancer. Conceptually, synthetic lethality ...
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2 HRR defects confer synthetic lethality to PARP inhibitors (PARPi) ...
Novel therapeutic approaches in chondrosarcoma.
(FUTURE MEDICINE LTD, 2017-03-01)
Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally ...
PARP inhibitors: Synthetic lethality in the clinic.
(AMER ASSOC ADVANCEMENT SCIENCE, 2017-03-17)
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors ...
Modeling Therapy Resistance in BRCA1/2-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ...