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Genomic landscape of platinum resistant and sensitive testicular cancers.
(NATURE PUBLISHING GROUP, 2020-05-04)
While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and ...
Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 E17K-Mutant, ER-Positive Metastatic Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2020-08-01)
PURPOSE: The activating mutation AKT1 E17K occurs in approximately 7% of estrogen receptor-positive (ER+) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability ...
A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.
(WILEY, 2020-06-04)
The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is ...
Transplantation of discarded livers following viability testing with normothermic machine perfusion.
(NATURE PORTFOLIO, 2020-06-16)
There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using ...
Olaparib for Metastatic Castration-Resistant Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2020-05-28)
BACKGROUND: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) ...
Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis.
(ELSEVIER, 2020-04-01)
BACKGROUND: Declines in prostate-specific antigen (PSA) levels at 12wk are used to evaluate treatment response in metastatic castration-resistant prostate cancer (mCRPC). PSA fall by ≥30% at 4wk (PSA4w30) has been reported ...
Impact of mitochondrial DNA mutations in multiple myeloma.
(NATURE PUBLISHING GROUP, 2020-05-01)
Integrative analysis of large-scale loss-of-function screens identifies robust cancer-associated genetic interactions.
(ELIFE SCIENCES PUBLICATIONS LTD, 2020-05-28)
Genetic interactions, including synthetic lethal effects, can now be systematically identified in cancer cell lines using high-throughput genetic perturbation screens. Despite this advance, few genetic interactions have ...
Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2020-10-01)
Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ...
Noninvasive MRI Native T1 Mapping Detects Response to MYCN-targeted Therapies in the Th-MYCN Model of Neuroblastoma.
(AMER ASSOC CANCER RESEARCH, 2020-08-15)
Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies ...