5 results match your criteria: "NY (R.F.D.); Translational Clinical Sciences[Affiliation]"
Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion.
Cancer Cell
November 2024
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSK), New York, NY 10065, USA; Breast Medicine Service, Department of Medicine, MSK, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address:
Article Synopsis
- Inhibiting CDK4/6 kinases has improved breast cancer outcomes, but only a small number of patients achieve long-term control of the disease.
- The study finds that loss of the TP53 gene and amplification of the MDM2 gene are linked to poor long-term outcomes in patients with metastatic hormone receptor-positive breast cancer.
- In laboratory models, losing p53 does not impact CDK4/6 activity but leads to changes in CDK2 that allow cancer cells to evade treatment, suggesting a need for combined inhibition of CDK4/6 and CDK2 for better responses in diverse cases of HR+ breast cancer.
Ponsegromab for the Treatment of Cancer Cachexia.
N Engl J Med
December 2024
From the Internal Medicine Research Unit (J.D.G., I.K., M.A.H., A.R.S.) and Clinical Pharmacology (R.Q.), Pfizer, Cambridge, MA; Duke Cancer Institute, Duke University Medical Center, Durham, NC (J.C.); Global Biometrics and Data Management, Pfizer R&D UK, Sandwich (S.M.C.), and Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh (M.F.) - both in the United Kingdom; Translational Clinical Sciences, Pfizer, Collegeville, PA (S.L.); Knight Cancer Institute, Oregon Health and Science University, Portland (E.J.R.); the Cancer Supportive Care Center, Shizuoka Cancer Center, Shizuoka (T.N.), and the Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto (K.T.) - both in Japan; Cedars-Sinai Medical Center, Los Angeles (A.E.H.); the Ottawa Hospital Cancer Centre, Ottawa (T.A.); Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY (R.F.D.); Translational Clinical Sciences, Pfizer, Groton, CT (C.A.N.); and the Internal Medicine Research Unit, Pfizer, Tampa, FL (M.R.).
Background: Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels.
View Article and Find Full Text PDFSpatial epigenome-transcriptome co-profiling of mammalian tissues.
Nature
April 2023
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution.
View Article and Find Full Text PDFAddressing unmet needs for people with cancer cachexia: recommendations from a multistakeholder workshop.
J Cachexia Sarcopenia Muscle
April 2022
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations.
Circ Heart Fail
April 2017
From the Department of Medicine, Stony Brook University, NY (J.B., C.E.H.); Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA (J.E.U.); Division of Cardiology, Inova Heart & Vascular Institute, Falls Church, VA (C.O'C.); Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S.); Division of Cardiology, University of Brescia and Civil Hospital, Italy (M.M.); Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S., C.Y.); Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); Division of Cardiology, University of California San Francisco (J.R.T.); Merck & Co., Kenilworth, NJ (H.S.B., J.K.); Gilead Sciences, Foster City, CA (G.B., J.H., C.S.); Amgen Inc., Thousand Oaks, CA (C.D., M.K.); Bristol-Myers Squibb, Princeton, NJ (M.M.D., M.D., R.J.F., P.M., S.M., C.R.); Bayer, Wuppertal, Germany (W.D., M.v.d.L.); Department of Cardiology, HELIOS Clinic Wuppertal, University Hospital Witten/Herdecke, Germany (W.D.); AstraZeneca, Gaithersburg, MD (R.F.-D., J.H., L.-M.G.); AstraZeneca, Gothenburg, Sweden (R.F.-D., J.H., L.-M.G.); Relypsa Inc., Redwood City, CA (D.G., M.M.); Vifor Pharma, Opfikon, Switzerland (U.-M.G.); Department of Cardiology, Nippon Medical School Musashi-Kosugi Hospital, Kawasaki, Japan (S.I.); Novartis Pharmaceuticals Inc., East Hanover, NJ (P.K.-M., V.S.); Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (C.J.L.); Bayer Pharma AG, Wuppertal, Germany (L.R.); Cardiology Division, Columbia University Medical Center, New York, NY (C.R.); Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT (A.S.); Moderna Therapeutics, Cambridge, MA (B.T.); Division of Cardiovascular and Renal Products, United States Food and Drug Administration, Silver Spring, MD (N.S.); Center for Cardiovascular Innovation, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.G.).
The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans.
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