A5048598383- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Acute Lymphoblastic Leukemia research
- Colorectal Cancer Treatments and Studies
- Chronic Lymphocytic Leukemia Research
- Breast Cancer Treatment Studies
- Lung Cancer Research Studies
- PARP inhibition in cancer therapy
- Chronic Myeloid Leukemia Treatments
- Cytomegalovirus and herpesvirus research
- Hematopoietic Stem Cell Transplantation
- Neuroblastoma Research and Treatments
- Acute Myeloid Leukemia Research
- Ovarian cancer diagnosis and treatment
- interferon and immune responses
- Alkaline Phosphatase Research Studies
- CRISPR and Genetic Engineering
- Genetic factors in colorectal cancer
- Childhood Cancer Survivors' Quality of Life
Telesta Therapeutics (Canada)
2024
Advisory Board Company (United States)
2024
Pfizer (United States)
2012-2021
University College London
2019
Institute of Cancer Research
2019
Belfast Health and Social Care Trust
2019
University College London Hospitals NHS Foundation Trust
2019
Université du Québec à Montréal
2019
University of Alabama at Birmingham
2018
Dana-Farber Cancer Institute
2010-2018
Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 CDK6), which promote progression from the G1 phase to S cell cycle. We assessed efficacy palbociclib (an inhibitor CDK4 CDK6) fulvestrant in advanced cancer.This 3 study involved 521 patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative that had relapsed or progressed during prior endocrine therapy. randomly assigned a 2:1 ratio receive placebo...
Purpose Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than single agent alone. EGF104900 compared the activity of alone or combination with trastuzumab patients ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC). Patients Methods MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either...
ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of on sensitivity to standard therapies two phase III randomized trials that represent development current for estrogen receptor-positive cancer.In a prospective-retrospective analysis, we available archived baseline plasma from SoFEA (Study Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens patients...
Purpose Lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human 2 (HER-2/ErbB2), is effective against HER-2–positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy lapatinib in HER-2–negative HER-2–uncharacterized MBC. Patients Methods Women with MBC were randomly assigned to first-line therapy paclitaxel 175 mg/m every 3 weeks plus 1,500 mg/d placebo. A preplanned retrospective evaluation HER-2...
To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer.In this phase II multicenter trial, primary objective was assessment tumor response rate gefitinib; secondary objectives included analysis pharmacodynamic biologic profiles healthy tissue.while phosphorylation mitogen-activated protein kinase inhibited both tissues, treatment induced p27 a decrease Ki67 skin but not tumors....
Abstract CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of heterogeneity is unknown. Here we use plasma samples from patients randomized phase III PALOMA-3 study inhibitor palbociclib and fulvestrant cancer show that relative change PIK3CA ctDNA after...
Abstract Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of CDK4/6 inhibitor palbociclib primary cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− received anastrozole 1 mg daily for 4 weeks (cycle 0; goserelin if premenopausal), followed by adding (125 on days...
Abstract Purpose: PD-0332991 is a selective inhibitor of the CDK4/6 kinases with ability to block retinoblastoma (Rb) phosphorylation in low nanomolar range. Here we investigate role inhibition human ovarian cancer. Experimental Design: We examined effects on proliferation, cell-cycle, apoptosis, and Rb using panel 40 established cancer cell lines. Molecular markers for response prediction, including p16 Rb, were studied gene expression profiling, Western blot, array CGH. Multiple drug...
About one third of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting. PENELOPE-B (NCT01864746) double-blind, placebo-controlled, phase III study women primary without pathological complete response...
PURPOSE CDK4/6 inhibitors are used to treat estrogen receptor (ER)–positive metastatic breast cancer (BC) in combination with endocrine therapy. PALLET is a phase II randomized trial that evaluated the effects of palbociclib plus letrozole as neoadjuvant PATIENTS AND METHODS Postmenopausal women ER-positive primary BC and tumors greater than or equal 2.0 cm were randomly assigned 3:2:2:2 (2.5 mg/d) for 14 weeks (A); 2 weeks, then (B); (C); weeks. Palbociclib 125 mg/d was administered orally...
Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown be synthetic lethal with loss function (LOF) ataxia telangiectasia-mutated (ATM) kinase, preclinical studies identified ATRi-sensitizing alterations in other DNA damage (DDR) genes. Here we report the results from module 1 an ongoing phase trial ATRi camonsertib (RP-3500) 120 patients advanced solid tumors harboring...
The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations improve decisions about incorporation of biomarker studies in early investigational drug trials. members reviewed trials, peer-reviewed literature, NCI and U.S. Food Administration (FDA) guidance documents, conducted a survey investigators determine practices challenges executing clinical trials new drugs development. This document provides standard...
Abstract Purpose: Biomarkers from two randomized phase III trials were analyzed to optimize selection of patients for lapatinib therapy. Experimental Design: In available breast cancer tissue EGF30001 (paclitaxel ± in HER-2-negative/unknown metastatic cancer, n = 579) and EGF100151 (capecitabine HER-2-positive 399), HER-2 gene amplification by fluorescence situ hybridization (FISH), mRNA reverse transcription-PCR (RT-PCR), protein expression HercepTest immunohistochemistry (IHC), epidermal...
Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human 2 (HER2) with activity in HER2-amplified metastatic breast cancer (MBC). Its role non-HER2-amplified MBC remains unclear. EGF30001, phase III trial lapatinib paclitaxel versus placebo, demonstrated does not significantly benefit HER2-negative or HER2-unselected patients MBC. Published data support interactions between steroid hormone peptide signaling. We hypothesized that molecular subgroups may exist within...
1015 Background: Lapatinib (L) is an oral, small-molecule inhibitor of EGFR and HER2 with a mechanism action distinct from that trastuzumab (T). Preclinical data suggest synergy between L T. We studied alone in combination T pts HER2+ MBC who progressed on Methods: Eligible women had received prior anthracycline taxane therapy, measurable lesions or bone-only disease, T-containing therapy. Pts were stratified by hormone receptor status visceral/nonvisceral then randomized to receive either...
A subgroup of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumors coexpresses p95HER2, a truncated HER2 that retains highly functional kinase domain but lacks the extracellular and results in intrinsic trastuzumab resistance. We hypothesized lapatinib, tyrosine inhibitor, would be active these tumors. have studied correlation between p95HER2 expression response to both preclinical models clinical setting.Two different animal were used for studies. Expression was...
Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that chemotherapy in a phase III trial.PEARL multicentre, randomised study which patients aromatase inhibitor (AI)-resistant MBC were included two consecutive cohorts. In cohort 1, 1 : to palbociclib exemestane or capecitabine. On discovering new evidence about...
PURPOSE To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features. METHODS Both somatic germline analyses were performed using an Food Drug Administration–authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 whom diagnosed PACC. For subset PACCs, whole-genome (WGS; n = 12) RNA (n 6) performed. RESULTS Eighteen (36.7%) PACCs harbored pathogenic variants in homologous...