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Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
Splicing dysregulation as a driver of breast cancer.
(BIOSCIENTIFICA LTD, 2018-09-01)
Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behaviour. Despite the success of targeted therapy approaches for breast ...
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
(W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)
BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ...
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
(AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)
Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.
(WILEY, 2017-09-01)
BACKGROUND: The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed ...
Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib.
(ELSEVIER SCIENCE BV, 2018-01-06)
UNLABELLED: Acquired drug resistance impacts the majority of patients being treated with tyrosine kinase inhibitors (TKIs) and remains a key challenge in modern anti-cancer therapy. The lack of clinically effective therapies ...
Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts.
(IMPACT JOURNALS LLC, 2016-12-06)
The majority of breast cancers are estrogen receptor positive (ER+). Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER+ breast cancers. ...
An In Vivo Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Chemotherapy remains the mainstay of treatment for advanced breast cancer; however, resistance is an inevitable event for the majority of patients with metastatic disease. Moreover, there is little information available ...
Src Is a Potential Therapeutic Target in Endocrine-Resistant Breast Cancer Exhibiting Low Estrogen Receptor-Mediated Transactivation.
(PUBLIC LIBRARY SCIENCE, 2016-06-16)
Despite the effectiveness of endocrine therapies in estrogen receptor positive (ER+) breast cancer, approximately 40% of patients relapse. Previously, we identified the Focal-adhesion kinase canonical pathway as a major ...
Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution.
(NATURE PUBLISHING GROUP, 2017-12-08)
Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...