A5036875036- Head and Neck Cancer Studies
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cervical Cancer and HPV Research
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Polyomavirus and related diseases
- Colorectal and Anal Carcinomas
- Tumors and Oncological Cases
- Radiomics and Machine Learning in Medical Imaging
- Head and Neck Surgical Oncology
- Cancer-related gene regulation
- Thyroid Cancer Diagnosis and Treatment
- CAR-T cell therapy research
- PI3K/AKT/mTOR signaling in cancer
- Nonmelanoma Skin Cancer Studies
- Oral and Maxillofacial Pathology
- Cutaneous Melanoma Detection and Management
- RNA modifications and cancer
- Plant Virus Research Studies
- Advanced Breast Cancer Therapies
- Oral Health Pathology and Treatment
Dana-Farber Cancer Institute
2016-2025
Boston University
2024-2025
Harvard University
2012-2025
Brigham and Women's Hospital
2019-2025
University of Colorado Denver
2023
Michigan United
2023
University of California, Los Angeles
2023
Seoul National University Hospital
2023
Samsung Medical Center
2023
Moffitt Cancer Center
2023
Ex vivo systems that incorporate features of the tumor microenvironment and model dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology development effective combination therapies. Here, we demonstrate ability interrogate ex ICB using murine- patient-derived organotypic spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse human tumors retain autologous lymphoid myeloid cell populations respond short-term three-dimensional microfluidic...
Everolimus, an inhibitor of the mammalian target rapamycin (mTOR), is effective in treating tumors harboring alterations mTOR pathway. Mechanisms resistance to everolimus remain undefined. Resistance developed a patient with metastatic anaplastic thyroid carcinoma after extraordinary 18-month response. Whole-exome sequencing pretreatment and drug-resistant revealed nonsense mutation TSC2, negative regulator mTOR, suggesting mechanism for exquisite sensitivity everolimus. The resistant tumor...
A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population metastatic cSCCs.We performed targeted sequencing 504 cancer-associated genes on lymph node metastases 29 patients with cSCC identified mutations somatic copy-number associated cSCC. We determined significantly mutated, deleted, amplified clinical variables.The genome is...
Novel approaches are needed to improve outcomes in patients with squamous cell carcinoma of the oral cavity. Neoadjuvant immunotherapy given prior surgery and combining programmed death protein 1 (PD-1) cytotoxic T-lymphocyte-associated 4 (CTLA-4) immune checkpoint inhibitors 2 strategies enhance antitumor responses that could be benefit.
Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result pathologic tumor response (pTR), lower the relapse rate resectable human papillomavirus (HPV)-unrelated HNSCC.Neoadjuvant (200 mg) was administered followed 2 3 weeks later by surgical ablation. Postoperative (chemo)radiation planned. Patients high-risk pathology (positive margins and/or...
Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating squamous carcinoma of the head and neck (SCCHN), but objective response rates are low. PD-1 ligand (PD-L1) expression alone is not considered a robust predictor additional biomarkers needed. This 3-year observational cohort followed 126 SCCHN patients treated with anti–PD-1/L1 therapy. Prior to treatment, 81 (64%) had targeted massively parallel tumor sequencing. Of these, 42 (52%) underwent fluorescence-activated...
Human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (OPSCC) is increasing in the United States. Current epidemiologic assessments of national burden HPV-positive OPSCC are needed.The Surveillance Epidemiology End Results HPV Status Database included 12,017 patients with pharyngeal subsites, including non-OPSCC cancer subsites (hypopharynx, nasopharynx, "other pharynx"), diagnosed from 2013 to 2014. Age-adjusted incidence rates per 100,000 persons by status...
Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy safety data exploratory biomarker analyses from cohort patients with mMCC treated first-line avelumab phase II trial.
About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration anti-programmed death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the microenvironment (TME). However, mechanisms underlying dynamics antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, approaches to increase are lacking. In a phase 2 trial (NCT02296684), we...
PURPOSE Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression necessary to prevent but may attenuate antitumor response with PD-1 inhibitors. METHODS We report a phase I study cemiplimab kidney (KTRs) CSCC. After cross-taper mammalian target rapamycin...
BackgroundMeasuring cell-free (cf)DNA in blood and tissues holds significant potential as a minimally invasive method for disease monitoring cancer. Cancers arising the oropharynx causally linked to human papillomavirus (HPV) represent an ideal model which interrogate these methods.Patients methodsWe designed ultrasensitive quantitative droplet digital (dd)PCR assay detect five dominant high-risk HPV subtypes oropharyngeal cancer (OPC). We enrolled pilot observational cohort of 22 patients...
Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy everolimus aggressive, radioactive iodine-refractory (RAIR) cancer and correlated tumor mutational profiling with response. Exploratory medullary anaplastic cohorts were included.Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 2013 patients incurable RAIR who had radiographic progression six months prior enrollment. The...
Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti-PD-1, nivolumab (N), anti-KIR, lirilumab (L)] before after salvage surgery to improve disease-free survival (DFS).
Human papillomavirus (HPV), most commonly HPV16, causes a growing subset of head and neck squamous cell carcinomas (HNSCCs), including the overwhelming majority oropharynx in many developed countries. Circulating biomarkers for HPV-positive HNSCC may allow earlier diagnosis, with potential to decrease morbidity mortality. This case-control study evaluated whether circulating tumor HPV DNA (ctHPVDNA) is detectable prediagnostic plasma from individuals later diagnosed HNSCC. Cases were...
Circulating tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA is a dynamic, clinically relevant biomarker for HPV-positive oropharyngeal squamous cell carcinoma. Reasons its wide pretreatment interpatient variability are not well understood.To characterize clinicopathologic factors associated with TTMV HPV DNA.This cross-sectional study included patients evaluated carcinoma at Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022 who...
CB-103 selectively inhibits the CSL-NICD (Notch intracellular domain) interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This dose-escalation/expansion study aimed determine safety, pharmacokinetics, and preliminary antitumor activity.
2538 Background: BDC-1001 is a HER2-targeted immune-stimulating antibody conjugate (ISAC), designed to trigger local activation of the innate immune system and generate durable tumor-targeted adaptive response. incorporates trastuzumab biosimilar (EG12014) conjugated proprietary TLR7/8 agonist using non-cleavable linker cell membrane-impermeable payload. An international phase 1/2 study was initiated evaluate safety ± nivolumab (nivo) identify recommended 2 dose (RP2D) considering PK/PD...
Abstract Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged a biomarker which can inform disease status during surveillance. Experimental Design: This retrospective observational cohort study involved 543 patients who completed...
Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive squamous cell carcinoma (OSCC), and no therapies have been shown affect its natural history. A recent study the PVL immune landscape revealed cytotoxic T-cell-rich microenvironment, providing strong rationale investigate checkpoint therapy.