A5056041412- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Prostate Cancer Diagnosis and Treatment
- Health Systems, Economic Evaluations, Quality of Life
- Genetic factors in colorectal cancer
- Science, Research, and Medicine
- Statistical Methods in Clinical Trials
- Lipoproteins and Cardiovascular Health
- Molecular Biology Techniques and Applications
- Metabolism, Diabetes, and Cancer
- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- Ferroptosis and cancer prognosis
- Radiomics and Machine Learning in Medical Imaging
- Genetic Associations and Epidemiology
- Nutrition, Genetics, and Disease
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Reliability and Agreement in Measurement
- DNA Repair Mechanisms
- Nutritional Studies and Diet
- Health and Wellbeing Research
- Genomics and Rare Diseases
Harvard University
2015-2025
Massachusetts General Hospital
2022-2025
Leibniz Institute for Prevention Research and Epidemiology - BIPS
2024-2025
Memorial Sloan Kettering Cancer Center
2018-2024
Harvard University Press
2024
University of Bremen
2024
Kettering University
2018-2023
Mayo Clinic
2015-2023
Dana-Farber Cancer Institute
2023
Public Health Department
2021
The genomic underpinning of clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer is unclear.
Alterations in DNA damage repair (DDR) genes occur up to 25% of patients with metastatic castration-resistant prostate cancer (mCRPC) and may sensitize platinum chemotherapy. We aimed evaluate the efficacy platinum-based chemotherapy DDR-mutant (DDRmut) mCRPC.We assessed response based on DDR gene alteration status men mCRPC who underwent tumor germline genomic profiling. Patients deleterious alterations a panel that included BRCA2, BRCA1, ATM, PALB2, FANCA, CDK12 were considered DDRmut.A...
Aneuploidy, defined as chromosome gains and losses, is a hallmark of cancer. However, compared with other tumor types, extensive aneuploidy relatively rare in prostate Thus, whether numerical aberrations dictate disease progression cancer patients not known. Here, we report the development method based on whole-transcriptome profiling that allowed us to identify chromosome-arm losses 333 primary tumors. In two independent cohorts (n = 404) followed prospectively for metastases...
Lethal prostate cancers have higher expression of squalene monooxygenase (SQLE), the second rate-limiting enzyme cholesterol synthesis. Preclinical studies suggested that aberrant regulators, receptors and transporters contribute to accumulation uniformly. We assessed their association with features aggressive cancers. In prospective cancer cohorts within Health Professional Follow-up Study, Physicians' Study Swedish Watchful Waiting tumor mRNA profiling was performed. disease defined as...
Abstract Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer have historically relied upon genome-wide markers, the adaptation targeted clinical sequencing panels presents an opportunity incorporate into routine diagnostic workflows. We show that global ancestral contributions and admixture continental populations can be quantitatively inferred using markers captured by MSK-IMPACT panel. In a...
Prostate cancer is the most heritable cancer. There a need to identify possible modifiable factors for men at an increased risk of prostate due genetic factors. To examine whether can offset their disease or progression by adhering healthy lifestyle. We prospectively followed 12 411 genotyped in Health Professionals Follow-up Study (1993–2019) and Physicians' (1983–2010). Genetic was quantified using polygenic score (PRS). A lifestyle defined weight, vigorous physical activity, not smoking,...
Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence limited some genes currently included in testing, panels are also likely to be incomplete and missing that influence PCa risk aggressive disease.
Abstract Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression cholesterol synthesis enzymes, transporters, and regulators tumor specimen at diagnosis lethal cancer, defined as mortality or metastases from contrast to nonlethal disease without evidence after least 8 years follow-up. We analyzed prospective cohorts within Health Professionals Follow-up Study (n = 249) Physicians' 153) well expectantly...
Abstract Background To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical molecular features. Methods A total 49,392 men from Health Professionals Follow-up Study (HPFS) were followed 1986 to 2014. Data on self-reported collected at baseline updated biennially. Clinical features included localised, advanced, lethal, low-grade, intermediate-grade, high-grade. Molecular TMPRSS2: ERG PTEN subtypes. Cox proportional hazards regression models...
Abstract Purpose: Oncogenic alterations of the PI3K/AKT pathway occur in >40% patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance other PI3K components cancer is largely unknown. Experimental Design: Patients this study underwent tumor sequencing using MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; structural rearrangements, or were profiled through Cancer...
Importance Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective To explore differences in risk early prostate higher vs lower to inform efforts. Design, Setting, and Participants This cohort study used combined analysis genotyped without at inclusion lifestyle data 2 prospective studies Sweden the US, Malmö Diet Cancer Study (MDCS) Health Professionals...
Among prostate cancers containing Gleason pattern 4, cribriform morphology is associated with unfavorable clinicopathologic factors, but its genetic features and association long-term outcomes are incompletely understood. In this study, genetic, transcriptional, epigenetic of invasive carcinoma (ICC) tumors were compared non-cribriform 4 (NC4) in The Cancer Genome Atlas (TCGA) cohort. ICC (
Abstract Background In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on outcome aggressive prostate cancer, but studies have defined this differently. We aimed develop an evidence-based consensus definition cancer using clinical features at diagnosis for epidemiologic research. Methods Among cases diagnosed in 2007 National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared...
Abstract Purpose: Statins are associated with lower risk of aggressive prostate cancer, but lethal cancer is understudied and contributing mechanisms unclear. We prospectively examined statins in the Health Professionals Follow-up Study (HPFS), tested associations molecular subtypes, integrated gene expression profiling to identify putative mechanisms. Experimental Design: Our study included 44,126 men cancer-free 1990, followed for incidence through 2014, statin use recorded on biennial...
Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, response to immune checkpoint blockade (ICB) in patients MSI-H/dMMR TMB-H without MSI [TMB-H/microsatellite stable (MSS)].