A5038280749- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Renal and related cancers
- DNA Repair Mechanisms
- RNA modifications and cancer
- 3D Printing in Biomedical Research
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- BRCA gene mutations in cancer
- Microfluidic and Bio-sensing Technologies
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Prostate Cancer Treatment and Research
- Renal cell carcinoma treatment
- Lung Cancer Research Studies
- Cancer, Lipids, and Metabolism
- Cancer therapeutics and mechanisms
- Pancreatic and Hepatic Oncology Research
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Melanoma and MAPK Pathways
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
- Colorectal Cancer Treatments and Studies
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Howard Hughes Medical Institute
2016-2025
Center for Cancer Research
2006-2025
Rambam Health Care Campus
2019-2024
Broad Institute
2009-2024
Sechenov University
2023
Imperial College London
2023
Dana-Farber/Harvard Cancer Center
2014-2021
University of Oxford
2021
Most patients with non–small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets epidermal growth factor receptor (EGFR). However, about 10 percent of a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity gefitinib are unknown.
Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup non-small-cell lung cancers, representing 2 to 7% such tumors. We explored the therapeutic efficacy inhibiting ALK tumors an early-phase clinical trial crizotinib (PF-02341066), orally available small-molecule inhibitor tyrosine kinase.After screening tumor samples from approximately 1500 patients with cancer for presence rearrangements, we identified 82 advanced ALK-positive disease who...
Alterations in cancer genomes strongly influence clinical responses to treatment and many instances are potent biomarkers for response drugs. The Genomics of Drug Sensitivity Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource information on drug sensitivity cells molecular markers response. Data freely available without restriction. GDSC currently contains data almost 75 000 experiments, describing 138 anticancer drugs across 700 cell lines. To identify response,...
Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis preclinical models. To investigate its role human cancer, we characterized EMT circulating (CTCs) from breast cancer patients. Rare primary simultaneously expressed and markers, but were highly enriched CTCs. Serial CTC monitoring 11 patients suggested an association CTCs with disease progression. In index patient, reversible shifts between these cell...
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature cancer. Using this information to guide development and application therapies in clinic is challenging. Here, we report how cancer-driven alterations identified 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, gene expression) can be mapped onto 1,001 molecularly annotated human cell lines correlated with sensitivity 265 drugs. We find...
The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is effective but limited by emergence drug-resistance mutations. Molecular characterization circulating tumor cells may provide a strategy for noninvasive serial monitoring genotypes during treatment.We captured highly purified from blood using microfluidic device containing microposts coated antibodies against epithelial cells. We performed EGFR...
Gefitinib (Iressa, Astra Zeneca Pharmaceuticals) is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR) and induces dramatic clinical responses in nonsmall cell lung cancers (NSCLCs) with activating mutations within EGFR domain. We report these mutant EGFRs selectively activate Akt signal transduction activator of transcription (STAT) signaling pathways, which promote survival, but have no effect on extracellular signal–regulated signaling, proliferation....
Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring nonhematological cancers. We previously demonstrated effectiveness microfluidic device, CTC-Chip, capturing these epithelial cell adhesion molecule (EpCAM)-expressing using antibody-coated microposts. Here, we describe high-throughput mixing herringbone-chip, or “HB-Chip,” which provides an enhanced platform CTC...
A multistage microfluidic chip is capable of sorting rare EpCAM + and − CTCs from cancer patients’ whole blood.
Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to reversible tyrosine inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation EGFR domain, T790M, conferring drug resistance, other cases mechanism underlying acquired resistance is unknown. In studying multiple sites NSCLCs, we detected T790M only small percentage...
The hCHK2 gene encodes the human homolog of yeast Cds1 and Rad53 G 2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations occur Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited TP53 gene. These observations suggest tumor suppressor conferring predisposition sarcoma, breast cancer, brain tumors, they also provide link between central role...
In a screen for gene copy-number changes in mouse mammary tumors, we identified tumor with small 350-kb amplicon from region that is syntenic to much larger locus amplified human cancers at chromosome 11q22. The contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila Yorkie (Yki), downstream effector Hippo(Hpo)-Salvador(Sav)-Warts(Wts) signaling cascade, recently flies as critical regulator cellular proliferation and apoptosis. nontransformed epithelial cells,...
Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that isolation, ex vivo culture, and characterization CTCs may provide an opportunity to noninvasively monitor changing patterns drug susceptibility individual as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six estrogen receptor-positive breast cancer. Three five lines tested were tumorigenic mice....