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Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial.
(AMER ASSOC CANCER RESEARCH, 2018-08-30)
Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. ...
Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-09-01)
Mutations in estrogen receptor alpha (ERα) that confer resistance to existing classes of endocrine therapies are detected in up to 30% of patients who have relapsed during endocrine treatments. Because a significant ...
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 ...
Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.
(BIOMED CENTRAL LTD, 2018-06-08)
BACKGROUND: Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth ...
Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.
(CELL PRESS, 2018-04-19)
The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, ...
Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.
(CELL PRESS, 2018-04-19)
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with ...
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-03-07)
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...
Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
(NATURE RESEARCH, 2018-09-25)
How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to ...
Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer.
(ELSEVIER SCI LTD, 2018-11-01)
BACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in ...
Constitutional mutation in CDKN2A is associated with long term survivorship in multiple myeloma: a case report.
(BMC, 2017-11-06)
BACKGROUND: Multiple Myeloma is a cancer of plasma cells associated with significantly reduced survival. Long term survivorship from myeloma is very rare and despite advances in its treatment the disease is generally ...