A5083315480- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- Cancer Genomics and Diagnostics
- Mathematical Biology Tumor Growth
- PARP inhibition in cancer therapy
- Urinary and Genital Oncology Studies
- Radiopharmaceutical Chemistry and Applications
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Renal cell carcinoma treatment
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Statistical Methods in Clinical Trials
- DNA Repair Mechanisms
- Hormonal and reproductive studies
- Prostate Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Evolution and Genetic Dynamics
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Cancer Research and Treatment
- HER2/EGFR in Cancer Research
- Science, Research, and Medicine
Moffitt Cancer Center
2016-2025
First Affiliated Hospital of Anhui Medical University
2025
Anhui Medical University
2025
Sun Yat-sen University
2023
Hainan Medical University
2023
Xijing Hospital
2009-2023
Air Force Medical University
2018-2023
University of South Florida
2022-2023
Chengde Medical University
2021
Nanjing Medical University
2010-2019
The data reported herein were accepted for assessment by the US Food and Drug Administration Biologics License Application under priority review to establish clinical benefit of durvalumab as second-line therapy locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent approval.To report a planned update safety efficacy patients with advanced/metastatic UC.This is an ongoing phase 1/2 open-label study 191 adult histologically cytologically confirmed UC whose disease...
BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients mCRPC associated a BRCA alteration treated rucaparib 600 mg twice daily the phase II TRITON2 study.We enrolled who progressed after one two lines of next-generation androgen receptor-directed therapy taxane-based chemotherapy for mCRPC. Efficacy safety populations included...
Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median ~16.5 months. We hypothesize time to progression (TTP) could be increased integrating evolutionary dynamics into therapy. developed game theory model using Lotka-Volterra equations three competing "species": androgen dependent, producing, and...
PURPOSE To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers microtubule-disrupting agent, monomethyl auristatin E, to cells express Nectin-4. METHODS EV-101 is phase I dose escalation/expansion study enrolled patients with Nectin-4–expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on ≥ 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death...
A new ecologically inspired paradigm in cancer treatment known as "adaptive therapy" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing significant population treatment-sensitive cells survive. These, turn, suppress proliferation the less-fit resistant populations. However, there remain several open challenges designing therapies, particularly extending these...
Background: Abiraterone acetate is an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC), but evolution of resistance inevitably leads to progression. We present a pilot study in which abiraterone dosing guided by evolution-informed mathematical models delay onset resistance. Methods: In the cohort, was stopped when PSA <50% pretreatment value and resumed returned baseline. Results are compared contemporaneous cohort who had >50% decline after initial...
19 Background: Deleterious germline or somatic HRRm are present in about 20% of mCRPC patients (pts). Preclinically, PARP-inhibition demonstrated synergism with AR-targeted therapy. BRCAAway is a biomarker pre-selected, multicenter, randomized, phase-2 trial which evaluated efficacy AR-inhibitor (i) vs PARPi combination first-line pts and/or mutations BRCA1/2 ATM. Methods: Eligibility required front-line no prior exposure to PARPi, ARi, chemotherapy for mCRPC, and washout antiandrogen,...
Abstract Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism androgen receptor pathway (ARP)–targeted therapy. This trial evaluated the efficacy ARP inhibitor versus PARP their combination as first-line therapy mCRPC HRRms. Patients and Methods: BRCAAway is a biomarker preselected,...
Neoadjuvant chemotherapy (NAC) followed by radical cystectomy improves survival compared with alone for patients bladder cancer. Although gemcitabine cisplatin has become a standard NAC regimen, dose-dense combination of methotrexate, vinblastine, doxorubicin, and (ddMVAC) is being adopted at some institutions.To assess the association neoadjuvant ddMVAC vs regimens downstaging overall among treated cancer.Cross-sectional analysis data extracted from medical records consecutive sample, after...
Integration of evolutionary dynamics into systemic therapy for metastatic cancers can prolong tumor control compared with standard maximum tolerated dose (MTD) strategies. Prior investigations have focused on monotherapy, but many clinical cancer treatments combine two or more drugs. Optimizing the in multidrug is challenging because complex cellular interactions and large parameter space potential variations drugs, doses, treatment schedules. However, also represents an opportunity to...
Abstract Intermittent androgen deprivation therapy (IADT) is an attractive treatment for biochemically recurrent prostate cancer (PCa), whereby cycling on and off can reduce cumulative dose limit toxicities. We simulate prostate-specific antigen (PSA) dynamics, with enrichment of PCa stem-like cell (PCaSC) during as a plausible mechanism resistance evolution. Simulated PCaSC proliferation patterns correlate longitudinal serum PSA measurements in 70 patients. Learning dynamics from each cycle...
Abstract Purpose: CDK12 inactivation in metastatic castration-resistant prostate cancer (mCRPC) may predict immunotherapy responses. This phase 2 trial evaluated the efficacy of immune checkpoint inhibitor (ICI) therapy patients with CDK12-altered mCRPC. Patients and Methods: Eligible had mCRPC deleterious alterations any prior therapies except ICI. Cohort A received ipilimumab (1 mg/kg) nivolumab (3 every 3 weeks for up to four cycles, followed by 480 mg 4 weeks. C alone nonprostate tumors...
// Minghui Wu 1 , Edward Seto 2 and Jingsong Zhang Department of Genitourinary Oncology Cancer Imaging Metabolism, H Lee Moffitt Center, Tampa, FL, USA Molecular Oncology, Correspondence to: Zhang, email: Keywords : SIRT6, E2F1, glycolysis, metabolism, HDAC1 Received September 27, 2014 Accepted February 20, 2015 Published March 14, Abstract The fast proliferation cancer cells requires reprogramming its energy metabolism with aerobic glycolysis as a major source. Sirt6, class III histone...
286 Background: Anti-PD-L1 immunotherapy has shown promising clinical activity in urothelial carcinoma (UC). We report on a planned update of efficacy and follow-up patients (pts) receiving durvalumab for the treatment locally advanced or metastatic UC. Methods: Pts received 10 mg/kg Q2W up to 12 months (mo), unacceptable toxicity confirmed progressive disease. Tumor PD-L1 expression was assessed using validated Ventana SP263 assay (PD-L1 high = TC ≥ 25% IC 25%). Primary endpoints were ORR...
Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes patients prostate cancer.
<h3>Importance</h3> Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) IT regimens compared TT among patients metastatic clear cell renal carcinoma (RCC). Generalizability of these findings in a real-world cohort outside clinical trial setting is unclear. <h3>Objective</h3> To assess the association TT, IT, OS RCC. <h3>Design, Setting, Participants</h3> This retrospective propensity-matched study...
Abiraterone acetate (AA) has been proven effective for metastatic castration-resistant prostate cancer (mCRPC), and it proposed that adaptive AA may reduce toxicity prolong time to progression, when compared continuous AA. We developed a simple quantitative model of prostate-specific antigen (PSA) dynamics evaluate (PCa) stem cell enrichment as plausible driver treatment resistance. The incorporated PCa cells, non-stem cells PSA during therapy. A leave-one-out analysis was used calibrate...