A5036139118- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Genetic factors in colorectal cancer
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- BRCA gene mutations in cancer
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Gastric Cancer Management and Outcomes
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Protein Kinase Regulation and GTPase Signaling
- Medical Imaging Techniques and Applications
- Brain Metastases and Treatment
- Peptidase Inhibition and Analysis
Memorial Sloan Kettering Cancer Center
2019-2025
Cornell University
2022-2024
Kettering University
2020-2024
CancerCare
2023
Massachusetts General Hospital
2018
Harvard University
2013-2015
Lemuel Shattuck Hospital
2014-2015
Brigham and Women's Hospital
2012-2014
Dana-Farber Cancer Institute
2012-2014
Dana-Farber Brigham Cancer Center
2012-2013
Abstract Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies primary and secondary resistance immunotherapy are multifaceted, deriving not from tumor intrinsic factors, also complex interplay between cancer its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories approaches design novel drugs combination therapies: first involves direct modification tumor, while second...
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....
Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than the general population, yet cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized.
With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, patient samples, we detected heterogeneous pattern putative alterations expected primarily to prevent inhibition ERK signaling by drugs at progression. Serial analysis blood samples on treatment demonstrates that most these are low frequency except for amplification, recurrent mechanism...
Abstract Background: Mutations in KRAS are among the most frequent oncogenic drivers with G12C mutation found up to ~13% of NSCLC. LY3537982 is an oral, highly selective, and potent inhibitor G12C, which preclinically delivers >90% sustained target occupancy. We present initial results from LOXO-RAS-20001, a phase 1 study patients (pts) G12C-mutant advanced solid tumors (NCT04956640). Methods: monotherapy dose escalation followed mTPI-2 method. Dose expansion cohorts included...
94 Background: LY3537982 is an oral, potent, and highly selective inhibitor of GDP-bound KRAS G12C with unique pharmacologic properties that achieve high target occupancy at low absolute exposures. Here we present results GI tumors treated on LOXO-RAS-20001, a phase 1 study in patients (pts) mutation. Methods: Dose escalation followed mTPI-2 method. expansion included combination cetuximab colorectal cancer (CRC). All pts were naïve. Key objectives to determine the RP2D, safety, PK,...
8510 Background: While immunotherapy (IO) is established as the cornerstone of first-line treatment for KRAS-mutant NSCLC, outcomes remain suboptimal. Further progress may be achieved with addition targeted therapy to IO, an paradigm in some other cancer types (RCC), but historically challenging NSCLC. Here, we study pembrolizumab plus olomorasib, a potent and highly selective second-generation inhibitor GDP-bound KRAS G12C, NSCLC patients treated on LOXO-RAS-20001, phase 1/2 olomorasib...
3007 Background: Olomorasib is a potent and highly selective second-generation inhibitor of GDP-bound KRAS G12C, which preclinically delivers >90% sustained target occupancy. Here, we report updated results from LOXO-RAS-20001, phase 1/2 study olomorasib in patients with G12C-mutant advanced solid tumors (NCT04956640). Methods: Patients (pts) positive for G12C (tissue or plasma) were eligible. Dose escalation used mTPI-2 method, followed by expansion cohorts NSCLC (with/without prior...
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Background Germline risk assessment is increasing as part of cancer care; however, disparities in subsequent genetic counseling are unknown. Methods Pan‐cancer patients were prospectively consented to tumor‐normal sequencing via custom next generation panel (Memorial Sloan Kettering‐Integrated Mutation Profiling Actionable Cancer Targets) inclusive germline analysis ≥76 genes from January 2015 through December 2019 (97.5% research nonbillable) with protocol for genetics referral. Rates...
Central nervous system (CNS) metastases develop in nearly half of patients with RET fusion-positive NSCLCs and cause morbidity mortality. The selective inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation is associated decreased development CNS metastases.
Abstract Background The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and examine risk factors for irAE admissions clinically relevant outcomes, including length stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, death. Methods Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any combination) at Massachusetts General Hospital (MGH) were MGH...
Abstract Purpose: KRAS G12C is the most common mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging activity of KRASG12C inhibitors metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features patients with surgically resected KRASG12C-mutant Experimental Design: Patients who underwent resection stage I–III adenocarcinoma next-generation sequencing (NGS) were evaluated. Exclusion criteria receipt induction therapy,...
Abstract The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas prostate, this confers sensitivity to PARP inhibitors platinum-therapies. Somatic reversion mutations restoring function mediate resistance, have exclusively been reported in tumors. study, we analyze matched tumor normal sequencing from 31,927 patients identify 846 (2.7%) with germline variants across 43...
Background Sensitive and reliable biomarkers for early detection of recurrence are needed to improve post-definitive radiation risk stratification, disease management, outcomes patients with unresectable early-stage or locally advanced non-small cell lung cancer (NSCLC) who treated definitive therapy (RT). This prospective, multistate single-center, cohort study investigated the association circulating tumor DNA (ctDNA) status in stage I-III NSCLC underwent RT. Methods A total 70 serial...