A5069777765- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- PI3K/AKT/mTOR signaling in cancer
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Cancer Treatment and Pharmacology
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Lymphoma Diagnosis and Treatment
- Adenosine and Purinergic Signaling
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Biosimilars and Bioanalytical Methods
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Research and Treatments
- PARP inhibition in cancer therapy
- Cancer, Stress, Anesthesia, and Immune Response
- Biochemical and Molecular Research
- Health Systems, Economic Evaluations, Quality of Life
- Peptidase Inhibition and Analysis
Sarah Cannon
2016-2025
HealthONE
2016-2025
Sarah Cannon Research Institute
2014-2023
The University of Texas MD Anderson Cancer Center
2012-2023
Weatherford College
2022
Presbyterian St. Luke's Medical Center
2014-2020
Dana-Farber Cancer Institute
2016-2019
Memorial Sloan Kettering Cancer Center
2016-2019
Rice University
2019
South Texas Accelerated Research Therapeutics
2012-2019
Resistance to therapy with BRAF kinase inhibitors is associated reactivation of the mitogen-activated protein (MAPK) pathway. To address this problem, we conducted a phase 1 and 2 trial combined treatment dabrafenib, selective inhibitor, trametinib, MAPK (MEK) inhibitor.
No therapies for targeting
Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors a phase 1 study, and particularly promising was observed subgroup of non–small-cell lung cancer (NSCLC).
In this first-in-human, Phase 1 study of a microRNA-based cancer therapy, the recommended 2 dose (RP2D) MRX34, liposomal mimic microRNA-34a (miR-34a), was determined and evaluated in patients with advanced solid tumours. Adults various tumours refractory to standard treatments were enrolled 3 + dose-escalation cohorts and, following RP2D determination, expansion cohorts. oral dexamethasone premedication, given intravenously daily for 5 days 3-week cycles. Common all-cause adverse events...
RET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with fusion-positive NSCLC, the efficacy and safety selective inhibition unknown.We enrolled advanced NSCLC who had previously received platinum-based chemotherapy those were untreated separately a phase 1-2 trial selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by independent review committee. Secondary points included duration...
Abstract Purpose: We initiated a personalized medicine program in the context of early clinical trials, using targeted agents matched with tumor molecular aberrations. Herein, we report our observations. Patient and Methods: Patients advanced cancer were treated Clinical Center for Targeted Therapy. Molecular analysis was conducted MD Anderson Laboratory Improvement Amendments (CLIA)–certified laboratory. whose tumors had an aberration therapy, when available. Treatment assignment not...
To evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, MEK in patients V600-mutant metastatic colorectal cancer (mCRC).A total of 43 mCRC were treated dabrafenib (150 mg twice daily) plus trametinib (2 daily), 17 whom enrolled onto pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues analyzed for microsatellite instability, PTEN status, 487-gene sequencing. Patient-derived xenografts established from core biopsy samples.Of...
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,...
PIK3CA mutations may predict response to PI3K/AKT/mTOR inhibitors in patients with advanced cancers, but the relevance of mutation subtype has not been investigated. Patients diverse cancers referred Clinical Center for Targeted Therapy were analyzed and, if possible, KRAS mutations. treated, whenever agents targeting pathway. Overall, 105 (10%) 1,012 tested harbored Sixty-six (median 3 prior therapies) PIK3CA-mutant patients, including 16 individuals (of 55 tested) simultaneous mutations,...
KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy sotorasib, a G12C inhibitor, previously treated patients with p.G12C–mutated cancer are unknown.
Purpose To report the overall survival (OS) and clinical characteristics of BRAF inhibitor–naive long-term responders survivors treated with dabrafenib plus trametinib in a phase I II study patients V600 mutation–positive metastatic melanoma. Methods 150 mg twice daily 2 (the 150/2 group) from non–randomly assigned (part B) randomly C) cohorts were analyzed for progression-free OS separately. Baseline factors on treatment associations durable responses OS. Results For groups (n = 78), at 1,...
To determine the maximum-tolerated dose (MTD) and assess safety, pharmacokinetics, pharmacodynamics, evidence of antitumor activity RO4929097, a gamma secretase inhibitor Notch signaling in patients with advanced solid malignancies.Patients received escalating doses RO4929097 orally on two schedules: (A) 3 consecutive days per week for 2 weeks every weeks; (B) 7 weeks. reversible CYP3A4 autoinduction, expanded part study tested three dosing as above; modified A, d/wk (C) continuous daily...
Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is recruit who, while having failed previous treatments, nevertheless respond molecularly targeted drugs. We report findings of prospective, single-center study conducted with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation...
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...
Background: Mutations of v-raf murine sarcoma viral oncogene homolog B (BRAF) are commonly identified in papillary and anaplastic thyroid carcinoma associated with worse prognosis compared the wild type. BRAF inhibition cell lines xenografts inhibits proliferation decreases downstream phosphorylation. Our objectives were to analyze safety efficacy selective inhibitor dabrafenib patients metastatic BRAF-mutant carcinoma. Methods: We present subset enrolled a larger phase 1 study, main results...
Abstract Purpose: The purpose of this study was to confirm our previous results that targeted agents matched with tumor molecular alterations were associated improved outcomes compared nonmatched therapy in patients advanced cancer. Experimental Design: Outcomes who referred for treatment on phase I clinical trials at University Texas MD Anderson Cancer Center (Houston, TX) from March 2011 January 2012 between those had received and whom no available. Two-month landmark analyses overall...
Purpose Interleukin-10 (IL-10) stimulates the expansion and cytotoxicity of tumor-infiltrating CD8+ T cells inhibits inflammatory CD4+ cells. Pegylation prolongs serum concentration IL-10 without changing immunologic profile. This phase I study sought to determine safety antitumor activity AM0010. Patients Methods with selected advanced solid tumors were treated AM0010 in a dose-escalation study, which was followed by renal cell cancer (RCC) dose-expansion cohort. self-administered...
Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF MEK inhibition is more effective in BRAF(V600)-mutant melanoma than single-agent inhibitors. This study assessed the safety efficacy of dabrafenib trametinib patients who had received prior inhibitor treatment.In this open-label phase I/II study, we evaluated pharmacology, safety, trametinib. Here, report treated combination after disease progression treatment administered before enrollment (part...
We conducted a first-in-human dose-escalation study with the oral FASN inhibitor TVB-2640 to determine maximum tolerated dose (MTD) and recommended phase 2 (RP2D), as monotherapy taxane.This completed open-label outpatient was at 11 sites in United States Kingdom. Patients previously-treated advanced metastatic solid tumors adequate performance status organ function were eligible. administered orally daily until PD. Dose escalation initially followed an accelerated titration design that...