A5029329131- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Immune Cell Function and Interaction
- Breast Cancer Treatment Studies
- IL-33, ST2, and ILC Pathways
- Advanced Breast Cancer Therapies
- Chemotherapy-induced cardiotoxicity and mitigation
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Chronic Myeloid Leukemia Treatments
- Cardiac, Anesthesia and Surgical Outcomes
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Gastric Cancer Management and Outcomes
- Metastasis and carcinoma case studies
- Gastrointestinal Tumor Research and Treatment
Memorial Sloan Kettering Cancer Center
2009-2021
Massachusetts Institute of Technology
2019
University of Utah
2019
Dana-Farber/Harvard Cancer Center
2019
CancerCare
2019
National Cancer Institute
2018-2019
Digital Research Alliance of Canada
2019
Allen Institute
2019
Koch Institute for Integrative Cancer Research At MIT
2019
University of North Carolina at Chapel Hill
2018-2019
Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single-cell RNA sequencing (RNA-seq) longitudinally profile dynamic shifts the distribution a genetically engineered mouse model lung adenocarcinoma. In this model, interferon-responsive more...
Natural killer (NK) cells inhibit tumor development in mouse models and their presence tumors correlates with patient survival. However, tumor-associated NK become dysfunctional; thus, stimulation of cancer is emerging as an attractive immunotherapeutic strategy. In a model lung adenocarcinoma, localized to stroma immature phenotypes low functional capacity. To test responsiveness within established disease, we engineered system for inducible expression activating ligands tumors. After...
Abstract #4104 Background: Dose dense (dd) q2wk AC-paclitaxel (P) is superior to q3wk AC-P. Both regimens are associated with a <1% incidence of CHF. In MBC, nanoparticle albumin-bound paclitaxel (nab-P) P and bevacizumab (B) improves progression-free survival when added P. Based on the MBC data, B may be more effective targeting minimal residual disease in adjuvant setting nab-P offer efficacy reduced toxicity. However, it uncertain whether AC plus increases risk We evaluated cardiac...
Abstract Heterogeneity among naive adaptive lymphocytes determines their individual functions and fate decisions during an immune response. NK cells are innate capable of generating “adaptive” responses infectious challenges. However, the factors that govern various cell not fully understood. In this study, we use a reporter mouse model to permanently “time stamp” type 1 lymphoid (ILC1s) characterize dynamics homeostatic turnover. We found turnover tissue-resident ILC1s is much slower than...
Abstract Purpose Dual HER2 targeting increases pathologic complete response (pCR) rate to neoadjuvant therapy and improves outcomes in both early metastatic HER2-positive disease. CALGB 40601 is a randomized phase III trial examining the impact of dual blockade consisting trastuzumab (H) lapatinib (L) added paclitaxel (T) on pCR, considering tumor microenvironment molecular features. We previously found that pCR was numerically but not significantly increased with therapy, subtype evidence...
518 Background: We showed that dd q 2 weekly (w) AC → P + T×1 year (y) as adjuvant treatment (Rx) for patients (pts) with HER2 (+) BCA is safe a congestive heart failure (CHF) rate of 1/70 pts (in press, JCO 2008). Lapatinib (L) effective in HER2/neu w/ Stage IV and being tested randomized trials. are conducting pilot study w T L to determine the cardiac safety feasibility this combination. The 1° endpoint defined discontinuation due 1) death or 2) CHF. 2° endpoints evaluate toxicities, time...
Abstract Background: D is an inhibitor of multiple tyrosine kinases; BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Pre-clinical data show inhibition BC cell lines; predominantly those “basal-like” subtype or “triple-negative” (TN) single agent activity has been seen in refractory MBC. In pre-clinical models, the combination P had antitumor that was significantly better than either alone. We designed this phase 1 trial to translate observation.Methods: Eligibility...
Abstract Background: Inhibition of SRC is a novel approach for MBC. D an inhibitor multiple tyrosine kinases, including the family. Pre-clinical data show inhibits breast cancer cell lines, those “basal-like” subtype. In preclinical models + P had superior antitumor activity to either agent alone. We designed this phase I-II study translate observation. Methods: For I: pts with MBC, ECOG PS 0-1, normal hepatic, renal, marrow function were eligible. Pts pleural/pericardial effusions excluded....
Abstract #4102 Background
 Dose-Dense (dd) doxorubicin-cyclophosphamide (AC)-paclitaxel (P) is superior to q3w AC-P. Both are associated with a <1% incidence of congestive heart failure (CHF). The advent targeted therapies potentially raises the risks cardiac toxicity. We have, therefore, conducted 3 sequential safety studies using ddAC → P, one which included bevacizumab (B) concurrently ddAC. Here we report alone or B.
 Methods
 Patients...
Abstract Background: A previous feasibility trial (E2104 – Ann Oncol 23(2):331–7,2012) suggested incorporation of B into anthracycline-containing adjuvant therapy was feasible but ongoing cardiac monitoring required to define the true impact on function. Methods: Patients (pts) were assigned 1:2:2 one three treatment arms. In addition doxorubicin and cyclophosphamide followed by weekly paclitaxel, patients received either placebo (Arm AC>T) or during chemotherapy - BAC>BT),...
1156 Background: Inhibition of SRC is a novel approach for MBC. Preclinically, the inhibitor D + P had superior antitumor activity to either agent alone. We designed this phase I-II study translate observation. Methods: For I: pts with MBC, ECOG PS 0-1, normal hepatic, renal, marrow function were eligible. Pts pleural/pericardial effusions excluded. II: measurable, HER2-negative ≤2 prior rx Cycle (C) consisted wP 80 mg/m2 IV 3/4 weeks 70mg orally daily; escalating 100 mg, 120 and 150 mg in...
637 Background: ddAC-paclitaxel (P) is superior to q3w AC-P. Both are associated w/ a <1% incidence of congestive heart failure (CHF). In multicenter studies adjuvant trastuzumab (T), pt dropout rate after ACx4 was 6.7 % due asymptomatic declines in LVEF (ALVEF). Per protocol, T w/held these pts although the long-term significance unknown. There similar concern for ALVEF B+AC. We conducted 3 sequential pilot trials ddAC alone or B and report changes post AC x4. Methods: Pts HER-2+ BC were...
ABSTRACT Regulatory T cells (T regs ) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. human tumors span diverse transcriptional states distinct from those of peripheral , but their contribution to tumor development remains unknown. Here, we used single cell RNA-Seq longitudinally profile conventional CD4 + conv a genetic mouse model lung adenocarcinoma. Tissue-infiltrating differed, highlighting divergent pathways activation during...
Abstract Background: APT is a single arm multicenter, phase II study of paclitaxel and trastuzumab. Patients with HER2+ breast cancer negative nodes tumor size &lt; 3 cm were eligible. Disease-free survival at 7 years was 93.3% only 4 distant recurrences. Characterizing intrinsic subtype immune profiles these smaller tumors may help us better understand if the biology different than larger that have been previously characterized. Methods: Intrinsic subtyping by PAM50 signatures PanCancer...
Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we used single cell RNA-Seq longitudinally profile conventional CD4+ (Tconv) a genetic mouse model lung adenocarcinoma. Tissue-infiltrating differed, highlighting divergent pathways activation during...
Abstract Background: In CALGB 40601 (Alliance, NCT00770809), a neoadjuvant phase III trial of paclitaxel and trastuzumab with or without lapatinib for 12 weeks patients HER2-positive breast cancer, 33% pretreatment tumors were Luminal A subtype, however, 69% post-treatment samples residual disease subtype. addition, 71% B (12/17) 67% HER2-Enriched (6/9) changed into A, while 80% (20/24) remained (Carey et al. J Clin Oncol. 2016). It is not known whether this shift to was transient permanent....