A5069961391- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Chronic Myeloid Leukemia Treatments
- Prostate Cancer Treatment and Research
- 3D Printing in Biomedical Research
- Lung Cancer Research Studies
- Chronic Lymphocytic Leukemia Research
- Cancer, Lipids, and Metabolism
- Lymphoma Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- Microfluidic and Bio-sensing Technologies
- Cancer Research and Treatments
- Renal and related cancers
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Molecular Biology Techniques and Applications
- Metastasis and carcinoma case studies
- Phagocytosis and Immune Regulation
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Advanced Breast Cancer Therapies
- Cancer Immunotherapy and Biomarkers
Center for Cancer Research
2009-2025
Harvard University
2016-2025
Massachusetts General Hospital
2016-2025
Dana-Farber/Harvard Cancer Center
2018-2022
Dana-Farber Cancer Institute
1998-2019
Yonsei University
2019
Howard Hughes Medical Institute
2010-2017
Montgomery General Hospital
2017
Brigham and Women's Hospital
2014
University of California, Los Angeles
2013
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...
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...
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.
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....
Circulating signals of drug resistance Cancer drugs often lose their effectiveness because tumors acquire genetic changes that confer resistance. Ideally, patients would be switched to a different before tumor growth resumes, but this requires early knowledge how arose. Miyamoto et al. have developed non-invasive method spot by sequencing RNA transcripts in single circulating cells (CTCs) (see the Perspective Nanus and Giannakakou). For example, prostate cancer patients, was triggered...
Rare circulating tumor cells (CTCs) are present in the blood of patients with metastatic epithelial cancers but have been difficult to measure routinely. We report a quantitative automated imaging system for analysis prostate CTCs, taking advantage prostate-specific antigen (PSA), unique tumor-associated marker. The specificity PSA staining enabled optimization criteria baseline image intensity, morphometric measurements, and integration multiple signals three-dimensional microfluidic...
Noncoding RNAs transcribed from DNA repeats in heterochromatin are expressed at surprisingly high levels tumors.
Highlights•Pancreatic CTCs can be enriched with antigen-agnostic microfluidic technology•Single-cell RNA sequencing of pancreatic reveals three distinct CTC populations•Extracellular matrix genes are highly expressed in mouse and human CTCs•The extracellular protein SPARC contributes to tumor metastasisSummaryCirculating cells (CTCs) shed from primary tumors into the bloodstream, mediating hematogenous spread cancer distant organs. To define their composition, we compared genome-wide...
Significance Metastasis is responsible for 90% of cancer-related deaths and driven by tumor cells circulating in blood. However, it believed that only individual can reach distant organs because multicellular clusters are too large to pass through narrow capillaries. Here, we collected evidence examining microscale devices, computational simulations, animals, which suggest this assumption incorrect, may transit capillaries unfolding into single-file chains. This previously unidentified cell...
Abstract Selective kinase inhibitors have had a substantial impact on the field of medical oncology. Whereas these agents can elicit dramatic clinical responses in some settings, their activity is generally limited to subset treated patients whose tumor cells harbor specific genetic lesion. We established an automated platform for examining sensitivity various molecularly targeted across large panel human tumor-derived cell lines identify additional genotype-correlated that may be clinically...
Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 lines derived from diverse epithelial cancers for sensitivity 14 kinase inhibitors. Most were ineffective against unselected but exhibited dramatic killing small nonoverlapping subsets. Cells with exquisite EGFR, HER2, MET, or BRAF marked activating mutations amplification the drug...
Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPis) selectively kill BRCA1/2-deficient cells, but their efficacy in BRCA-deficient patients is limited by drug resistance. Here, we used derived cell lines and cells from to investigate how overcome PARPi We found that the functions of BRCA1 homologous recombination (HR) replication fork protection are sequentially bypassed during acquisition Despite lack BRCA1, PARPi-resistant regain RAD51 loading DNA double-stranded breaks (DSBs) stalled...
Purpose: The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation TKIs that overcome T790M-associated resistance available, noninvasive approaches detection will critical guide management.Experimental Design: part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis 40 patients with tumors progressing on...