A5023245303- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Breast Cancer Treatment Studies
- Immunotherapy and Immune Responses
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Monoclonal and Polyclonal Antibodies Research
- Genetic factors in colorectal cancer
- Radiomics and Machine Learning in Medical Imaging
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Bioinformatics and Genomic Networks
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
University of California, San Francisco
2016-2025
City College of San Francisco
2018-2024
Cancer Research Institute
2004-2023
UCSF Helen Diller Family Comprehensive Cancer Center
2008-2021
George Mason University
2016-2019
Georgetown University
2019
Quantum Leap Healthcare Collaborative
2017-2019
The University of Texas MD Anderson Cancer Center
2019
Philadelphia University
2019
University of Pennsylvania
2017-2019
The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of
Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk metastatic recurrence.Cell-free (cfDNA) was isolated from 291 plasma samples 84 high-risk early breast cancer patients treated in I-SPY 2 TRIAL standard NAC alone or combined MK-2206 (AKT inhibitor) treatment. Blood collected at pretreatment (T0), 3 weeks after initiation...
The principal reason for failure of targeted cancer therapies is the emergence resistant clones that regenerate tumor. Therapeutic efficacy therefore depends on not only how effectively a drug inhibits its target, but also innate or adaptive functional redundancy target and attendant pathway. In this regard, Myc transcription factors are intriguing therapeutic targets because they serve unique irreplaceable role coordinating expression many diverse genes that, together, required somatic cell...
Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond hormone receptor (HR) human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess predictive performance of mechanism-of-action biomarkers ∼990 patients treated with 10 regimens targeting diverse biology. explore >11 subtyping schemas...
Abstract The signature features of pancreatic ductal adenocarcinoma (PDAC) are its fibroinflammatory stroma, poor immune activity, and dismal prognosis. We show that acute activation Myc in indolent intraepithelial neoplasm (PanIN) epithelial cells vivo is, alone, sufficient to trigger immediate release instructive signals together coordinate changes multiple stromal immune-cell types drive transition adenocarcinomas share all the characteristic their spontaneous human counterpart. also...
Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized hormone receptor (HR)-positive/HER2-negative triple-negative (TNBC) patients receiving neoadjuvant chemotherapy (NAC) I-SPY2 trial. positivity rates before, during, after NAC are higher TNBC than HR-positive/HER2-negative patients. Early...
Although induction of blood vessel growth is acknowledged as a pivotal requirement for the evolution macroscopic tumors, events that trigger onset tumor angiogenesis remain largely obscure. The pervasive Myc oncoprotein itself potent inducer in wide range tissues. We have used reversibly switchable mouse transgenic model Myc-dependent β-cell carcinogenesis to delineate kinetics and causal sequence angiogenic processes following acute activation. show endothelial cell proliferation induced...
The ubiquitous deregulation of Myc in human cancers makes it an intriguing therapeutic target, a notion supported by recent studies Ras-driven lung tumors showing that inhibiting endogenous triggers tumor regression. However, neither the mechanism nor applicability inhibition to other types driven oncogenic mechanisms is established. Here, we show also regression simian virus 40 (SV40)-driven pancreatic islet model. Such presaged collapse microenvironment and involution vasculature. Hence,...
Gliomas are the most common primary tumours affecting adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in human majority of glioblastomas have elevated levels. Using dominant negative Omomyc, we previously showed that inhibition a promising strategy for cancer Here, preclinically validate as therapeutic mouse glioma, using model spontaneous multifocal invasive astrocytoma its derived neuroprogenitors, glioblastoma cell lines, patient-derived...
c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators in this process are members Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible c-Myc-induced whereas bax-deficient resistant. However, despite requirement for Bax, activation exerts no detectable effects on Bax expression, localization, or conformation. Moreover, susceptibility can be restored cells ectopic...
MdmX, also known as Mdm4, is a critical negative regulator of p53, and its overexpression serves to block p53 tumor suppressor function in many cancers. Consequently, inhibiting MdmX has emerged an attractive approach restoring those cancers that retain functional p53. However, the consequences acute systemic inhibition normal adult tissues remain unknown. To determine directly effects tumors, we crossed mdmX −/− mice into p53ER TAM knockin background. In place wild-type express variant ,...
Abstract Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy triple negative signature. However, not all patients achieved pathologic complete response and some HR+HER2− responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1 ness, CIN70 expression signatures; PARP1 protein) performed on 116 HER2− (VC: 72...
Abstract HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two combinations neoadjuvant I-SPY2 phase 2 adaptive platform trial for cancer at high risk recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2 + cancer, adaptively randomized to T-DM1/P, THP, or a common control arm paclitaxel/trastuzumab (TH), followed by...
Abstract We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction pathologic complete response (pCR) estimation recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). examined correlations between ctDNA FTV, evaluated the additive value FTV-based predictors pCR using area under curve (AUC) analysis, analyzed impact FTV on distant...