Clinical features of patients with -deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. and mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes.

Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study.

Background: Patients with metastatic urothelial carcinoma (mUC) have poor prognosis, so further development of novel combinations for these patients is needed.

Objective: To assess the safety and efficacy of eribulin mesylate (eribulin) with avelumab in mUC.

Design, Setting, And Participants: This was an open-label, phase 1b study in which patients with mUC who were cisplatin-ineligible and treatment-naïve or platinum-resistant were treated with eribulin and avelumab.

Alterations of DNA damage response genes correlate with response and overall survival in anti-PD-1/PD-L1-treated advanced urothelial cancer.

DNA damage response (DDR) gene alterations in cancer are associated with a higher tumor mutational burden (TMB) and may impact clinical outcomes of urothelial cancer (UC). Here, we explore the prognostic role of DDR alterations in advanced UC treated with anti-PD-1/PD-L1 agents. The study included 53 patients who had FoundationOne genomic sequencing and received anti-PD-1/PD-L1 therapy.

Prognostic Value of DNA Damage Response Genomic Alterations in Relapsed/Advanced Urothelial Cancer.

Background: DNA damage response (DDR) genomic alterations may play an important role in clinical outcomes of patients with urothelial cancer (UC). However, data on the prognostic role of DDR gene alterations in patients with advanced UC remain unclear.

Materials And Methods: We retrospectively collected data of three independent patient cohorts with relapsed or advanced UC including 81 and 91 patients from four institutions who underwent FoundationOne genomic sequencing as well as 129 patients selected from The Cancer Genome Atlas bladder cohort.

Temporal and spatial trends and determinants of aggressive prostate cancer among Black and White men with prostate cancer.

Purpose: Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA).

Methods: Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004-2014.

Mitotic activity in noninvasive papillary urothelial carcinoma: its value in predicting tumor recurrence and comparison with the contemporary 2-tier grading system.

Measures of mitotic activity predict behavior of noninvasive papillary urothelial carcinoma of the urinary bladder, but it is unclear what role these should have in tumor grading. In this article, we compare measures of mitotic activity to contemporary tumor grading, specifically in their association with recurrence of noninvasive papillary urothelial carcinoma. The study uses a retrospective cohort of 199 tumors from 124 patients.

The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors.

Multiple therapies currently exist for renal cell carcinoma, however, most do not result in cure and the development of acquired resistance is the rule rather than the exception. CDK4/6 and PIM1 kinases are potential new therapeutic targets in RCC. Abemaciclib is a potent CDK4/6 and PIM1 kinase inhibitor, thus we evaluated the effects of abemaciclib on renal cell carcinoma.

Molecular Characterization of Bladder Cancer in Smokers versus Nonsmokers.

Unlabelled: Smoking is considered an important risk factor for bladder cancer (BC), yet molecular characterization of BC in nonsmokers has not been extensively studied. Here, we compare molecular differences between smokers and nonsmokers with BC. BC specimens (676) profiled at a Clinical Laboratory Improvement Amendments-certified laboratory from 2006 to 2014 were retrospectively evaluated for molecular differences between smokers and nonsmokers.

Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma.

Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets.

Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis.

Background: Platinum-based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle-invasive bladder cancer patients. We performed a systematic review and meta-analysis to provide updated results of previous findings. We also summarized published data to compare clinical outcomes of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) versus gemcitabine and cisplatin/carboplatin (GC) in the neoadjuvant setting.

A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells.

Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population.

Current Immunotherapies for Renal Cell Carcinoma.

Immunotherapy, though not a new modality for cancer treatment, has enjoyed renewed vigor and interest over the last several years. Multiple new targets have been identified, and therapeutic agents are in varying stages of development, with some agents having obtained regulatory approval for administration in the clinic. Renal cell carcinoma is known to potentially respond favorably to immunotherapy, with a small subset of patients achieving durable responses to high dose interleukin-2 therapy.

Therapeutic approach guided by genetic alteration: use of MTOR inhibitor in renal medullary carcinoma with loss of PTEN expression.

Renal Medullary Cancer (RMC) is a rare and aggressive type of renal cell cancer that presents predominantly in patients with sickle cell hemoglobinopathies, and is typically metastatic at the time of presentation. Although platinum based chemotherapeutic regimens have recently emerged as the best option for producing a clinically significant response as reported in various case series, the response is far from satisfactory, as most RMC patients still succumb to their disease within a year of diagnosis. There is currently no standard of care for treatment of this disease.

PIM1 kinase as a target in prostate cancer: roles in tumorigenesis, castration resistance, and docetaxel resistance.

PIM1 kinase is a serine/threonine kinase that has been shown to be overexpressed in multiple human malignancies, including prostate cancer. PIM1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Increased PIM1 can also facilitate genomic instability to promote neoplastic processes.

Comparative molecular field analysis of flavonoid inhibitors of the PIM-1 kinase.

The PIM-1 protein, the product of the pim-1 oncogene, is a serine/threonine kinase. Dysregulation of the PIM-1 kinase has been implicated in the development of human malignancies including lymphomas, leukemias, and prostate cancer. Comparative molecular field analysis (CoMFA) is a 3-D QSAR technique that has been widely used, with notable success, to correlate biological activity with the steric and electrostatic properties of ligands.

Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase.

The pim-1 kinase is a true oncogene that has been implicated in the development of leukemias, lymphomas, and prostate cancer, and is the target of drug development programs. We have used experimental approaches to identify a selective, cell-permeable, small-molecule inhibitor of the pim-1 kinase to foster basic and translational studies of the enzyme. We used an ELISA-based kinase assay to screen a diversity library of potential kinase inhibitors.