A5084993667- Breast Cancer Treatment Studies
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Immune cells in cancer
- Lung Cancer Treatments and Mutations
- Gene expression and cancer classification
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Neutropenia and Cancer Infections
- Nutrition, Genetics, and Disease
- BRCA gene mutations in cancer
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Cancer Mechanisms and Therapy
- Breast Lesions and Carcinomas
- Advanced Biosensing Techniques and Applications
- Mechanisms of cancer metastasis
- Cancer, Lipids, and Metabolism
Royal Marsden Hospital
2015-2025
Breast Cancer Now
2015-2023
Institute of Cancer Research
2015-2023
Royal Marsden NHS Foundation Trust
2019-2021
AstraZeneca (Brazil)
2019
Clovis Oncology (United Kingdom)
2019
Novartis (Switzerland)
2019
Roche (Switzerland)
2019
Pfizer (United States)
2019
Queen Mary University of London
2012-2019
Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice.
Background: Estimating distant recurrence (DR) risk among women with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)–negative early breast cancer helps decisions on using adjuvant chemotherapy. The 21-gene Oncotype DX score (RS) is widely used for this. EndoPredict (EPclin) an alternative test combining prognostic information from eight-gene signature (EP score) tumor size and nodal status. We compared the provided by RS EPclin 10-year DR risk. Methods:...
The Onco
EndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin estimating 10-year distant recurrence-free interval (DRFI) rates those who received (ET) compared plus (ET + C). A total 3746 women were included in this joint analysis. 2630 5 years ET (ABCSG-6/8, TransATAC) and 1116 C (GEICAM 2003-02/9906). The primary...
Phosphoinositide 3-kinase (PI3K) signaling is well established as important in cancer. To date most studies have been focused on the PI3K/p110α isoform, which has found to be mutated several different cancers. The aim of our study was determine specific PI3K isoforms are involved pancreatic ductal adenocarcinoma (PDAC) and investigate effects these proliferation, survival, induction Akt activation cancer cells.The expression all downstream targets analyzed by immunohistochemistry human...
Abstract Purpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression selected genes prior implications prognosis treatment resistance. secondary determine prognostic impact residual disease genes' expression. Experimental Design: Expression levels 24 were quantified NanoString nCounter on formalin-fixed paraffin-embedded tumors from 126 NAC and 56 paired...
Abstract Purpose: To identify the individual genes or gene modules that lead to OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby indices of residual risk may guide selection patients for extended adjuvant therapy. Experimental Design: We conducted a retrospective assessment relationship between (i) Recurrence Score (ii) early (0–5 years) late (5–10 rates in 1,125 postmenopausal with primary estrogen receptor–positive breast cancer treated anastrozole...
Abstract Introduction: Currently, risk of recurrence in ER+ HER2- breast cancer is determined by pathological stage and histological grade, combination with a Gene Expression Assay (GEA) including Oncotype, Prosigna, Breast Cancer Index EPClin. Higher disease justifies systemic therapy beyond endocrine alone. GEAs need improving as these assays can misclassify risk, i.e., recurrences still occur patients assigned low risk. Thus, approaches to identify high-risk cases more accurately would...
The scattering response of epithelial cells to activation the Met receptor tyrosine kinase represents one facet an "invasive growth" program. It is a complex event that incorporates loss cell-cell adhesion, morphological changes, and cell motility. Ubiquitination reversible posttranslational modification may target proteins for degradation or coordinate signal transduction pathways. There are approximately 79 active deubiquitinating enzymes (DUBs) predicted in human genome. Here, via small...
Understanding the factors, which control ErbB2 and EGF receptor (EGFR) status in cells is likely to inform future therapeutic approaches directed at these potent oncogenes. resistant stimulus-induced degradation high levels of over-expression can inhibit down-regulation. We now show that for HeLa expressing similar numbers EGFR ErbB2, down-regulation efficient insensitive reduction levels. Deubiquitinating enzymes (DUBs) may extend protein half-lives by rescuing ubiquitinated substrates from...
The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect expression of hormone-regulated and proliferation-associated genes (PAGs) premenopausal ER+ breast cancer. Whilst previous studies demonstrated differences gene expression, here, we investigated if there are within patient oestrogen- progesterone-regulated (ERGs PRGs) PAGs cancer during cycle. Samples from 96 patients two independent prospective effect on were used. Plasma measurements...
Abstract Purpose: Invasive lobular carcinoma (ILC) accounts for approximately 5%–15% of all invasive breast cancer cases. Most the correlations between multigene assays and patient outcome were derived from studies based on patients with ductal (IDC) or without distinction subtypes. Here, we investigate prognostic value EndoPredict (EPclin) in a large cohort ILCs pooled three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC). Experimental Design: The primary objective this analysis...
// Anissa Chikh 1,* , Riccardo Ferro Jonathan J. Abbott 1 Roberto Piñeiro Richard Buus Manuela Iezzi 3 Francesca Ricci 4 Daniele Bergamaschi Paola Ostano 5 Giovanna Chiorino Rossano Lattanzio 2,3 Massimo Broggini Mauro Piantelli Tania Maffucci and Marco Falasca 1,6 Queen Mary University of London, Barts The London School Medicine Dentistry, Blizard Institute, Centre for Cell Biology Cutaneous Research, UK 2 Department Medical, Oral Biotechnological Sciences, “G....
To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)-resistant triple-negative breast cancer (TNBC) and ER+HER2- disease.
Abstract Purpose: To investigate the presence of ESR1 mutations in primary estrogen-receptor–positive (ER+) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from inhibition (AI) alone based upon on-treatment changes gene expression. Experimental Design: We evaluated ER, progesterone receptor, Ki67 by immunostaining, droplet-digital PCR expression over 800 key genes paired pre-...
Background The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC ATC) has proven challenging to treat, survival beyond a few months from diagnosis is rare. Although 30%–60% these tumors contain mutations in the BRAF gene, inhibitors designed specifically target oncogenic have shown limited only short-lasting therapeutic benefits as single agents, thus highlighting need for improved treatment strategies, including novel combinations. Methods Using...
Abstract Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe development validation methods recapitulate RS, EP ROR scores from NanoString expression data. RNA was available 107 tumours postmenopausal women early-stage, ER+, HER2− cancer...
Several thousand breast cancer patients develop resistance to aromatase inhibitors (AIs) each year in the UK. Rational treatment requires an improved molecular characterisation of resistant disease. The mutational landscape 198 regions 16 key genes and RNA expression 209 covering pathways was evaluated paired biopsies before AI at progression on from 48 patients. Validity findings assessed another five ESR1-mutated tumours progressing AI. Eighty-nine mutations were identified 41 matched...
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by high frequency loss-of-function
Systemic relapse after radiotherapy and surgery is the major cause of disease-related mortality in sarcoma patients. Combining immunotherapy under investigation as a means to improve response rates. However, immune contexture understudied. Here, we use retrospective cohort patients, treated with neoadjuvant radiotherapy, TCGA data. We explore therapeutic targets relevance sarcoma, using genomics multispectral immunohistochemistry provide insights into tumor microenvironment across subtypes....
Highlights•Prior chemotherapy treatment of mice enhances metastatic colonization and outgrowth•Chemotherapy induces SASP expression in normal tissues cultured cells•Chemotherapy fibroblast senescence sensitivity to navitoclax cultureSummaryDisseminated tumor cells frequently exhibit a period dormancy, rendering them insensitive; conversely, the systemic delivery chemotherapies can result tissue damage. Using multiple mouse human breast cancer models, we demonstrate that prior administration...
Abstract Background: A number of prognostic signatures have been developed for the prediction breast cancer recurrence in past decade. We two (Clinical Treatment Score (CTS), four immunohistochemical markers (IHC4)) and validated (Oncotype Dx Recurrence (RS), PAM50-based Prosigna (ROR), Breast Cancer Index (BCI), EndoPredict (EPclin)) TransATAC cohort. Here, we compare performance these six distant (DR) years 0-10, specifically 5-10 after treatment cessation. Methods: 1231 postmenopausal...