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CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer.
(2016-07)
Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast ...
Development of molecularly targeted agents and immunotherapies in small cell lung cancer.
(ELSEVIER SCI LTD, 2016-06-01)
Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination ...
The genomic landscape of testicular germ cell tumours: from susceptibility to treatment.
(NATURE PUBLISHING GROUP, 2016-07-01)
The genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk ...
Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer.
(ELSEVIER SCIENCE BV, 2016-11-01)
BACKGROUND: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen ...
Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer.
(ELSEVIER SCI LTD, 2016-05-01)
Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing ...
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(AMER CHEMICAL SOC, 2016-10-27)
The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ...
Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases.
(ELIFE SCIENCES PUBLICATIONS LTD, 2016-12-09)
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility ...
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 ...
Critical parameters in targeted drug development: the pharmacological audit trail.
(W B SAUNDERS CO-ELSEVIER INC, 2016-08-01)
The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) ...
Drug discovery in advanced prostate cancer: translating biology into therapy.
(NATURE PUBLISHING GROUP, 2016-10-01)
Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology ...