A5102972148- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Breast Cancer Treatment Studies
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Economic and Financial Impacts of Cancer
- Cancer, Hypoxia, and Metabolism
- Health Systems, Economic Evaluations, Quality of Life
- Colorectal Cancer Treatments and Studies
- Lung Cancer Research Studies
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Breast Lesions and Carcinomas
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Chronic Myeloid Leukemia Treatments
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Genetic factors in colorectal cancer
The University of Texas MD Anderson Cancer Center
2015-2024
Breast Cancer Care
2004-2023
Advanced Cancer Therapeutics
2009-2023
Eli Lilly (United States)
2022
The University of Texas Health Science Center at Houston
2016-2019
Mayo Clinic
2018
Ludwig-Maximilians-Universität München
2017
Pfizer (United States)
2017
Institute of Cancer Research
2017
Sarcoma Oncology Center
2013
A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than alone in the initial treatment of postmenopausal women estrogen-receptor (ER)–positive, human epidermal growth factor receptor (HER2)–negative advanced breast cancer. We performed a 3 designed to confirm and expand efficacy safety data for this indication.
Mutations of the PIK3CA gene may predict response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) inhibitors. Concomitant mutations in mitogen-activated protein kinase (MAPK) pathway mediate resistance.Tumors from patients with breast, cervical, endometrial, and ovarian cancer referred Clinical Center for Targeted Therapy (Phase I Program) were analyzed PIK3CA, KRAS, NRAS, BRAF mutations. Patients treated, whenever feasible, agents targeting PI3K/AKT/mTOR...
Preclinical data suggest that PIK3CA mutations predict response to PI3K/AKT/mTOR inhibitors. Concomitant KRAS or BRAF may mediate resistance. Therefore, tumors from patients referred the phase I program for targeted therapy starting in October 2008 were analyzed using PCR-based DNA sequencing of exons 9 and 20. Consecutive with diverse tumor types mutation treated whenever possible agents targeting pathway. Overall, detected 25 217 (11.5%; exon 9, n = 11; 20, 14). In more than 10 tested,...
Resistance to neoadjuvant chemotherapy in triple-negative breast cancer can be mediated by a reversible chemotherapy-tolerant state.
Despite a wealth of preclinical studies, it is unclear whether PIK3CA or phosphatase and tensin homolog (PTEN) gene aberrations are actionable in the clinical setting. Of 1,656 patients with advanced, refractory cancers tested for PTEN abnormalities, mutations were found 9% (146/1,589), loss and/or mutation was 13% (149/1,157). In multicovariable analysis, treatment phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) inhibitor only independent factor predicting...
BackgroundTargeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis.Patients and methodsWe developed comprehensive assay targeting 9223 CpG sites consistently hypermethylated according The Cancer Genome Atlas. Next, we carried out clinical validation our method using cfDNA samples from 78 advanced colorectal cancer, non-small-cell...
Abstract Most triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary tumors TNBC patients diagnosed synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated tracking reveal robust alterations architecture...
507 Background: Hormonal therapy (HT) is the mainstay for patients (pts) with ER+ BC. P, a cyclin-dependent kinase 4/6 inhibitor, blocks growth of ER+/HER2– BC preclinical models. In PALOMA-1, an open-label Ph 2 trial, addition P to L improved median PFS vs alone (20.2 months [mo] 10.2 mo) in pts first-line ABC acceptable safety, leading accelerated FDA approval. PALOMA-2 randomized double-blind 3 trial designed confirm these results. Methods: 666 postmenopausal no prior systemic were 2:1...
Further advances of targeted cancer therapy require comprehensive in-depth profiling somatic mutations that are present in subpopulations tumor cells a clinical sample. However, it is unclear to what extent such intratumor heterogeneity and whether may affect decision-making. To study this question, we established deep sequencing platform identify potentially actionable DNA alterations samples.We assayed 515 formalin-fixed paraffin-embedded (FFPE) samples matched germline (475 patients) from...
BackgroundThis report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) or without visceral metastases.Patients methodsPre- postmenopausal disease progression following prior ET (PALOMA-3; N= 521) untreated for ABC (PALOMA-2; 666) were randomized 2:1 to (fulvestrant letrozole, respectively) placebo. Progression-free survival (PFS), safety,...
Abstract Purpose: Standard-of-care treatment for metastatic hormone receptor–positive (HR+), HER2-negative (HER2−) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, that has recently demonstrated significant overall survival benefit in two phase III trials, combination everolimus and exemestane patients HR+, HER2− advanced (ABC) CDK4/6i....
PIK3CA mutations are frequently diagnosed in diverse cancers and may predict response to PI3K/AKT/mTOR inhibitors. It remains unclear whether they associated with other characteristics. We analyzed characteristics outcome of 90 consecutive patients advanced tumors 180 wild-type controls matched by tumor type, gender, age referred the Clinical Center for Targeted Therapy. MAPK (KRAS, NRAS, BRAF) were using polymerase chain reaction-based DNA sequencing. The most frequent E545K (31/90, 34%),...
Abstract Purpose: This dose-finding phase I study investigated the maximum-tolerated dose (MTD) and safety of weekly nanoparticle albumin-bound rapamycin (nab-rapamycin) in patients with untreatable advanced nonhematologic malignancies. Experimental Design: nab-Rapamycin was administered for 3 weeks followed by 1 week rest, a starting 45 mg/m2. Additional doses were 56.25, 100, 150, 125 Results: Of 27 enrolled patients, 26 treated. Two dose-limiting toxicities (DLT) occurred at 150 mg/m2...
We evaluated the safety, maximum tolerated dose, pharmacokinetics, and biological effects of combination Raf-1, RET, KIT, platelet-derived growth factor receptor, vascular endothelial receptor 2 kinase inhibitor sorafenib farnesyltransferase tipifarnib.A standard 3 + phase I dose-escalation design was used with a 28-day cycle (sorafenib daily tipifarnib for 21 days, by mouth).Fifty patients were treated; 43 reached restaging evaluation after 2. The most common side grade 1 to rash,...
The aim of this study was to assess the frequency potentially actionable genomic alterations in breast cancer that could be targeted with approved agents or investigational drugs clinical trials using a next-generation sequencing-based profiling assay performed Clinical Laboratory Improvement Amendments-certified and College American Pathologists-accredited commercial laboratory. Methods. Fifty-one cancers were analyzed, including primary tumor biopsies 33 stage I-II 18 IV (13 soft tissue, 3...
Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose this study was assess relationship between increased pCR rate and trial-level benefit in triple-negative breast cancer (TNBC).We used bootstrap resampling from trial simulate trials with different rates. We estimates Adjuvant!Online populations baseline prognosis estimated improvements associated changes rate.Assuming...
// Jennifer J. Wheler 1 , Barbara A. Parker 2 Jack Lee 3 Johnique T. Atkins Filip Janku Apostolia M. Tsimberidou Ralph Zinner Vivek Subbiah Siqing Fu Richard Schwab Stacy Moulder 4 Vicente Valero Maria Schwaederle 5 Roman Yelensky 6 Vincent Miller M Philip Stephens Funda Meric-Bernstam Razelle Kurzrock Department of Investigational Cancer Therapeutics (Phase I Program), The University Texas MD Anderson Center, Houston, TX Center for Personalized Therapy and Division Hematology Oncology,...