A5043833554- Sarcoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Vascular Tumors and Angiosarcomas
- CAR-T cell therapy research
- Gastrointestinal Tumor Research and Treatment
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- Cardiac tumors and thrombi
- Histone Deacetylase Inhibitors Research
- Lymphoma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Colorectal and Anal Carcinomas
- Viral-associated cancers and disorders
- Gastric Cancer Management and Outcomes
- Colorectal Cancer Treatments and Studies
- Tuberous Sclerosis Complex Research
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Renal cell carcinoma treatment
- Immunotherapy and Immune Responses
- Ocular Oncology and Treatments
- Hedgehog Signaling Pathway Studies
- Histiocytic Disorders and Treatments
Memorial Sloan Kettering Cancer Center
2016-2025
Cornell University
2016-2025
Weill Cornell Medicine
2025
Kettering University
2009-2024
Daiichi Sankyo (Germany)
2016-2021
Daiichi-Sankyo (South Korea)
2016-2021
Astellas Pharma (China)
2021
Exelixis (United States)
2021
Roche (Switzerland)
2016-2021
Bioscience Research
2021
Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by process termed senescence. Progressive telomere shortening appears to trigger senescence normal fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase alone is insufficient enable certain other evade senescence, however. Such including keratinocytes mammary appear require loss...
Purpose Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab outside of clinical trials to determine the frequency use systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy effect these therapies on overall survival (OS) time failure (TTF). Patients Methods retrospectively medical records patients melanoma who had received between...
Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated predisposition. The recent success of immunotherapy high-frequency MSI (MSI-H) MMR-D tumors now supports all advanced solid tumors. extent which LS accounts MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence according status.MSI status was...
Uveal melanoma is characterized by mutations in GNAQ and GNA11, resulting mitogen-activated protein kinase pathway activation.To assess the efficacy of selumetinib, a selective, non-adenosine triphosphate competitive inhibitor MEK1 MEK2, uveal melanoma.Randomized, open-label, phase 2 clinical trial comparing selumetinib vs chemotherapy conducted from August 2010 through December 2013 among 120 patients with metastatic at 15 academic oncology centers United States Canada.One hundred one were...
CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth induces senescence cell lines xenografts. In a phase I trial PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label II study to determine the safety efficacy advanced WDLS/DDLS.
More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective and CDK6 inhibitor palbociclib inhibits growth induces senescence in liposarcoma cell lines xenografts. Our prior phase 2 study demonstrated that treatment with (200 mg daily for 14 days every 21 days) resulted clinical benefit WD/DDLS but moderate hematologic toxic effects. It is important to understand whether at a new dose schedule-125 28 days-results manageable...
Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, mAbs cause cutaneous immune-related adverse events. Although the most commonly reported toxicities are mild, a subset persist despite therapy can lead to severe or life-threatening toxicity. Autoimmune blistering disorders not associated with mAb therapy. We...
This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo.A total 33 patients retinoblastoma protein-positive advanced solid tumours or non-Hodgkin's lymphoma refractory to standard therapy for which no was available received 0332991 once daily (QD) 14 days followed by 7 off treatment (21-day cycles; Schedule...
Perivascular epithelioid cell neoplasms (PEComa) are a family of rare mesenchymal tumors with hybrid myo-melanocytic differentiation. Although most PEComas harbor loss-of-function TSC1/TSC2 mutations, small subset were reported to carry TFE3 gene rearrangements. As no comprehensive genomic study has addressed the molecular classification PEComa, we sought investigate by multiple methodologies incidence and spectrum genetic abnormalities their potential genotype-phenotype correlations in...
<h3>Importance</h3> Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming. <h3>Objective</h3> To examine whether T-VEC in combination pembrolizumab is associated increased tumor-infiltrating lymphocyte infiltration programmed death-ligand 1 expression thus antitumor activity patients locally or metastatic sarcoma. <h3>Design, Setting,...
Abstract The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification therapeutic targets, research, advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or few subtypes. Herein, we report comparative analysis 2,138 representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable...
Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, with no approved treatment. To our knowledge, this phase II, single-arm, registration trial the first prospective clinical in disease, investigating safety and efficacy of mammalian target rapamycin inhibitor
Abstract There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome challenge by providing insight into sarcomas’ molecular drivers. Through targeted panel sequencing 7494 sarcomas representing 44 histologies, we identify highly recurrent type-specific alterations that aid in diagnosis treatment decisions. Sequencing lead to refinement or reassignment...
The cell cycle governs the transition from quiescence through growth to proliferation. key parts of machinery are cyclin-dependent kinases (cdks) and regulatory proteins called cyclins. cdks rational targets for cancer therapy because their expression in cells is often aberrant inhibition can induce death. Inhibitors also block transcription. Several drugs targeting have entered clinical trials. These agents include flavopiridol, indisulam, AZD5438, SNS-032, bryostatin-1, seliciclib, PD...
BACKGROUND Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T‐lymphocyte–associated protein 4 (anti‐CTLA‐4) antibody ipilimumab standard care for metastatic melanoma; however, the clinical activity CTLA‐4 inhibition in patients with uveal poorly defined. METHODS To assess this setting, authors performed multicenter, retrospective analysis hospitals United States and Europe. Clinical...
Preclinical studies have shown synergistic antitumour activity by inhibition of insulin-like growth factor-1 receptor (IGF-1R) and mTOR. The expression IGF-1R seems to be crucial for this effect. We investigated the safety efficacy combination antibody cixutumumab mTOR inhibitor temsirolimus in patients with chemotherapy-refractory bone soft-tissue sarcomas according immunohistochemistry.We undertook a multicentre, open-label, phase 2 study 19 cancer centres USA. Patients aged at least 16...
Abstract The outcome of patients with mucosal melanoma treated ipilimumab is not defined. To assess the efficacy and safety in this subset, we performed a multicenter, retrospective analysis 33 unresectable or metastatic ipilimumab. clinical characteristics, treatments, toxicities, radiographic assessment disease burden by central radiology review at each site, mutational profiles patients' tumors were recorded. Available peripheral blood samples used to humoral immunity against panel...
Purpose We evaluated the pharmacokinetics (PKs), pharmacodynamics, safety, and efficacy of selinexor, an oral selective inhibitor nuclear export compound, in patients with advanced soft tissue or bone sarcoma progressive disease. Patients Methods Fifty-four were treated selinexor twice per week (on days 1 3) at one three doses (30 mg/m 2 , 50 flat dose 60 mg) either continuously on a schedule 3 weeks on, off. PK analysis was performed under fasting fed states (low v high fat content) using...
Abstract Purpose: Sphingosine 1-phosphate (S1P) is an important mediator of cancer cell growth and proliferation. Production S1P catalyzed by sphingosine kinase 1 (SphK). Safingol, (l-threo-dihydrosphingosine) a putative inhibitor SphK. We conducted phase I trial safingol (S) alone in combination with cisplatin (C). Experimental Design: A 3 + dose escalation was used. For safety, S given week before the combination. C were then administered every weeks. over 60 to 120 minutes, depending on...
Research has demonstrated that icon arrays (also called "pictographs") are an effective method of communicating risk statistics and appear particularly useful to less numerate graphically literate people. Yet research is very limited regarding whether type affects how people interpret remember these graphs.1502 age 35-75 from a demographically diverse online panel completed cardiovascular calculator based on Framingham data using their actual age, weight, other health data. Participants...
// Marta Kovatcheva 1,5,* , David D. Liu 2,5,* Mark A. Dickson 3,7 Mary E. Klein 1,5 Rachael O’Connor 8 Fatima O. Wilder Nicholas Socci 6 William Tap Gary K. Schwartz 7,9 Samuel Singer Aimee M. Crago 5,8 and Andrew Koff 1,2,5 1 The Louis V. Gerstner Graduate School of Biomedical Sciences, Sloan-Kettering Institute, Memorial Cancer Center, New York, USA 2 Program in Biochemistry, Cellular Molecular Biology, Weill College Medicine, Cornell University, 3 Department 4 Surgery, 5...