Timothy A. Chan
A5080223712- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Renal and related cancers
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Salivary Gland Tumors Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
- Brain Metastases and Treatment
- Ferroptosis and cancer prognosis
- Ovarian cancer diagnosis and treatment
- Cell Adhesion Molecules Research
- Lung Cancer Treatments and Mutations
- Neuroblastoma Research and Treatments
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Thyroid Cancer Diagnosis and Treatment
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
Cleveland Clinic
2020-2025
Case Western Reserve University
2020-2025
Cleveland Clinic Lerner College of Medicine
2020-2025
Columbia University Irving Medical Center
2011-2025
Center for Neuroscience and Regenerative Medicine
2021-2024
Case Comprehensive Cancer Center
2020-2024
Kiang Wu Hospital
2024
Emory University
2024
University of Toronto
2024
Howard Hughes Medical Institute
1998-2023
Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response this therapy, we used whole-exome sequencing non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated improved objective response, durable clinical benefit, and progression-free survival....
Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit unknown. Ipilimumab and tremelimumab antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells enables them to destroy tumor cells.We obtained tissue from melanoma who were treated ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors matched blood...
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
<h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of cancer. Here, we describe genomic landscape 496 PTCs. We observed a low frequency somatic alterations (relative to other carcinomas) and extended set known PTC driver include <i>EIF1AX</i>, <i>PPM1D</i>, <i>CHEK2</i> diverse gene fusions. These discoveries reduced fraction cases with unknown oncogenic from 25% 3.5%. Combined analyses variants, expression, methylation demonstrated that different groups lead...
PPARB was identified as a target of APC through the analysis global gene expression profiles in human colorectal cancer (CRC) cells. PPARdelta elevated CRCs and repressed by CRC This repression mediated beta-catenin/Tcf-4-responsive elements promotor. The ability PPARs to bind eicosanoids suggested that might be chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPARdelta-responsive were NSAID sulindac. Furthermore, sulindac able disrupt its recognition...
HLA genotype affects response Immunotherapy works by activating the patient's own immune system to fight cancer. For effective tumor killing, CD8 + T cells recognize peptides presented human leukocyte antigen class I (HLA-I) molecules. In humans, there are three major HLA-I genes ( HLA-A, HLA-B , and HLA-C ). Chowell et al. asked whether germline influences how respond checkpoint inhibitor immunotherapies (see Perspective Kvistborg Yewdell). They examined more than 1500 patients found that...
Tumor-infiltrating immune cells have been linked to prognosis and response immunotherapy; however, the levels of distinct cell subsets signals that draw them into a tumor, such as expression antigen presenting machinery genes, remain poorly characterized. Here, we employ gene expression-based computational method profile infiltration 24 populations in 19 cancer types. We compare types using an score T find clear renal carcinoma (ccRCC) is among highest for both scores. Using profiles well...
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress immuno-oncology will require detailed understanding infiltrative landscape found these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA)...
Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis durable remission metastatic bladder cancer patient treated with everolimus, drug that inhibits mTOR (mammalian target rapamycin) signaling pathway. Among somatic mutations was loss-of-function mutation TSC1 (tuberous sclerosis complex 1), regulator pathway activation. Targeted revealed about 8% 109 additional cancers examined, and correlated...
Nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit colorectal tumorigenesis and are among the few agents known to be useful for chemoprevention of neoplasia. Here, we show that tumor suppressive effects NSAIDs not likely related a reduction in prostaglandins but rather due elevation prostaglandin precursor arachidonic acid (AA). NSAID treatment colon cells results dramatic increase AA turn stimulates conversion sphingomyelin ceramide, mediator apoptosis. These have significant...
Tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations. This high mutational burden renders tumors immunogenic sensitive to programmed cell death-1 (PD-1) immune checkpoint inhibitors. Yet, despite their tumor immunogenicity, patients MMR-deficient experience highly variable responses, roughly half refractory treatment. We present experimental clinical evidence showing that the degree...
Expression of 14-3-3 σ (σ) is induced in response to DNA damage, and causes cells arrest G 2 . By SAGE (serial analysis gene expression) analysis, we identified as a whose expression 7-fold lower breast carcinoma than normal epithelium. We verified this finding by Northern blot analysis. Remarkably, mRNA was undetectable 45 48 primary carcinomas. Genetic alterations at such loss heterozygosity were rare (1/20 informative cases), no mutations detected (0/34). On the other hand,...