A5042115782- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Lung Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Gastric Cancer Management and Outcomes
- Genetic factors in colorectal cancer
- Cancer Mechanisms and Therapy
- Brain Metastases and Treatment
- Endometrial and Cervical Cancer Treatments
- Ovarian cancer diagnosis and treatment
- Cancer Treatment and Pharmacology
- Melanoma and MAPK Pathways
- Radiopharmaceutical Chemistry and Applications
- Financial Markets and Investment Strategies
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
Memorial Sloan Kettering Cancer Center
2016-2025
Cornell University
2015-2024
Kettering University
2016-2024
Weill Cornell Medicine
2020-2024
Presbyterian Hospital
2024
358 (Finland)
2023
Faculty of 1000 (United States)
2023
Mirati Therapeutics (United States)
2022
Weatherford College
2022
Howard Hughes Medical Institute
2022
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).
Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma, but the fraction who derive clinical benefit remains undefined. Here, we report experience 860 metastatic adenocarcinoma analyzed prospectively mutations in >300 cancer-associated genes. Potentially actionable events were stratified into one four levels based upon published or laboratory evidence that mutation question confers increased sensitivity to investigational therapies. Overall, 37.1% (319/860)...
Purpose Human epidermal growth factor receptor 2 ( HER2, ERBB2)-activating mutations occur in 2% of lung cancers. We assessed the activity ado-trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, cohort patients with HER2-mutant cancers as part phase II basket trial. Patients and Methods received emtansine at 3.6 mg/kg intravenously every 3 weeks until progression. The primary end point was overall response rate using Response Evaluation Criteria Solid Tumors (RECIST) version 1.1....
Most patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC) experience clinical benefit from selective KRASG12C inhibition, whereas colorectal bearing the same mutation rarely respond. To investigate cause of limited efficacy inhibitors in cancer, we examined effects AMG510 G12C lines. Unlike NSCLC lines, models have high basal receptor tyrosine kinase (RTK) activation and are responsive to growth factor stimulation. In inhibition induces higher phospho-ERK rebound than cells....
Abstract Most mutations in cancer are rare, which complicates the identification of therapeutically significant and thus limits clinical impact genomic profiling patients with cancer. Here, we analyzed 24,592 cancers including 10,336 prospectively sequenced advanced disease to identify mutant residues arising more frequently than expected absence selection. We identified 1,165 statistically hotspot 80% arose 1 1,000 or fewer patients. Of 55 recurrent in-frame indels, validated that novel...
Ulixertinib (BVD-523) is an ERK1/2 kinase inhibitor with potent preclinical activity in BRAF- and RAS-mutant cell lines. In this multicenter phase I trial (NCT01781429), 135 patients were enrolled to accelerated 3 + dose-escalation cohort six distinct dose-expansion cohorts. Dose escalation included 27 patients, dosed from 10 900 mg twice daily established the recommended II dose (RP2D) of 600 daily. exposure was proportional RP2D, which provided near-complete inhibition ERK whole blood....
Abstract Purpose: Tumor mutation burden (TMB) is a biomarker of response to immune checkpoint blockade (ICB). The impact TMB on outcomes with targeted therapies has not been explored. Experimental Design: We identified all patients metastatic EGFR exon19del or L858R-mutant lung cancers treated first/second-generation tyrosine kinase inhibitors (TKIs) pretreatment next-generation sequencing data (MSK-IMPACT assay). effect time-to-treatment discontinuation (TTD) and overall survival (OS) were...
HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability activity of novel antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, vomiting. Two drug-related TEAEs associated fatal outcomes....
Highly aggressive thoracic neoplasms characterized by SMARCA4 (BRG1) deficiency and undifferentiated round cell or rhabdoid morphology have been recently described proposed to represent sarcomas. However, it remains unclear whether such tumors may instead sarcomatoid carcinomas, how their clinicopathologic characteristics compare with those of nonsarcomatoid SMARCA4-deficient non-small lung carcinomas (SD-NSCC).We identified 22 (SD-TSTs) and/or 45 SD-NSCCs, comprehensively analyzed...
To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and novel mechanisms drug resistance, we molecularly profiled
Amplification of and oncogenic mutations in ERBB2, the gene encoding HER2 receptor tyrosine kinase, promote hyperactivation tumor growth. Here we demonstrate that ubiquitination internalization, rather than its overexpression, are key mechanisms underlying endocytosis consequent efficacy anti-HER2 antibody-drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) trastuzumab deruxtecan (T-DXd) lung cancer cell lines patient-derived xenograft models. These data translated into a 51% response...
In ret proto-oncogene (RET)-rearranged lung cancers, data on the frequency of brain metastases and, in particular, outcomes multikinase inhibitor therapy patients with intracranial disease are not well characterized.A global, multi-institutional registry (cohort A, n = 114) and a bi-institutional set B, 71) RET-rearranged cancer were analyzed. Patients eligible if they had stage IV cancers harboring RET rearrangement by local testing. The incidence determined.The at time diagnosis was 25%...
Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis cfDNA Examine Somatic Status), an NGS assay for detection very low frequency alterations in 129 genes. Analytical validation demonstrated 92% sensitivity de-novo mutation calling down 0.5% allele and 99% a priori profiling. To evaluate the performance MSK-ACCESS, report results 681 prospective...