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E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-04-01)
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-01-01)
Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. ...
Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
(CELL PRESS, 2018-01-30)
Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically ...
Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.
(ELSEVIER SCI LTD, 2019-11-01)
INTRODUCTION: The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced ...
A decade of clinical development of PARP inhibitors in perspective.
(ELSEVIER, 2019-09-01)
Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ...
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
(SPRINGERNATURE, 2023-09-01)
Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ...
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
(ELSEVIER, 2022-08-01)
BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ...
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 ...
Synthetic lethality: the road to novel therapies for breast cancer.
(BIOSCIENTIFICA LTD, 2016-10-01)
When the BRCA1 and BRCA2 tumour suppressor genes were identified in the early 1990s, the immediate implications of mapping, cloning and delineating the sequence of these genes were that individuals in families with a BRCA ...
A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics.
(AMER ASSOC CANCER RESEARCH, 2019-01-01)
The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterize this heterogeneous disease by combining transcriptomics and genomics data, with the ...