The Brennen laboratory takes a rigorous, multi-disciplinary, team-based approach towards develo...ping innovative therapeutic and prognostic strategies for prostate cancer with an emphasis on exploiting vulnerabilities within the tumor microenvironment towards this goal. To accomplish this goal, we are strategically pursuing novel therapeutic platforms, including stromal-targeted prodrugs, protoxins, and radiolabeled antibodies, in addition to cell-based therapy and drug delivery; all of which are designed to reduce toxicity to peripheral non-target tissue (i.e. side effects) while maximizing anti-tumor efficacy (i.e. therapeutic benefit). Currently, many of these strategies are focused on overcoming stromal barriers to anti-tumor immune responses such that men suffering from prostate cancer can share in the immense, revolutionary power of immunotherapy that is transforming care for many with advanced disease in other tumor types previously thought to be unmanageable using conventional approaches. Unfortunately, prostate cancer has largely proven refractory to these powerful approaches thus far and requires novel mono- or combinatorial treatment strategies to unleash the full potential of the immune system and generate personalized anti-tumor responses with the capability of producing long-term durable responses or even cures in these men. view more

Research in the Craig Pollack Lab focuses on cancer prevention and control, particularly prosta...te cancer. Our work aims to understand how the organization environment of health care affects the type and quality of care that patients receive. Other work investigates the broader social context of health and health care— specifically housing, financial hardship and socioeconomic status. view more

The Artemov lab is within the Division of Cancer Imaging Research in the Department of Radiolog...y and Radiological Science. The lab focuses on 1) Use of advanced dynamic contrast enhanced-MRI and activated dual-contrast MRI to perform image-guided combination therapy of triple negative breast cancer and to assess therapeutic response. 2) Development of noninvasive MR markers of cell viability based on a dual-contrast technique that enables simultaneous tracking and monitoring of viability of transplanted stems cells in vivo. 3) Development of Tc-99m and Ga-68 angiogenic SPECT/PET tracers to image expression of VEGF receptors that are involved in tumor angiogenesis and can be important therapeutic targets. 4) Development of the concept of “click therapy” that combines advantages of multi-component targeting, bio-orthogonal conjugation and image guidance and preclinical validation in breast and prostate cancer models. view more

The Shenderov Lab focuses on the elucidation of the mechanisms of immune response and resistanc...e to immunotherapy in Prostate Cancer. This has led to clinical and basic research investigating the presumptive checkpoint inhibitor B7-H3.

In pursuit of understanding biomarkers or resistance and response, and regulatory molecules of immune response, we utilize artificial intelligence, immunogenomics, and spatial proteomics and transcriptomics in the laboratory and at the bedside using clinical trial correlative samples. view more

The main research goals of my laboratory are: (1) to identify and study the biology of novel ca...ncer selective targets whose enzymatic function can be exploited for therapeutic and diagnostic purposes; (2) to develop methods to target novel agents for activiation by these cancer selective targets while avoiding or minimizing systemic toxicity; (3) to develop novel agents for imaging cancer sites at earliest stages. To accomplish these objectives the lab has originally focused on the development of prodrugs or protoxins that are inactive when given systemically via the blood and only become activated by tumor or tissue specific proteases present within sites of tumor. Using this approach, we are developing therapies targeted for activation by the serine proteases prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2) and fibroblast activation protein (FAP) as well as the membrane carboxypeptidase prostate-specific membrane antigen (PSMA). One such approach developed in the lab consists of a potent bacterial protoxin that we have reengineered to be selectively activated by PSA within the Prostate. This PSA-activated toxin is currently being tested clinically as treatment for men with recurrent prostate cancer following radiation therapy. In a related approach, a novel peptide-cytotoxin prodrug candidate that is activated by PSMA has been identified and is this prodrug candidate is now entering early phase clinical development. In addition, we have also identified a series of potent inhibitors of PSA that are now under study as drug targeting and imaging agents to be used in the treatment and detection of prostate cancer.
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The Shawn Lupold Laboratory studies the biology of urologic malignancies, like prostate cancer,... to create new experimental diagnostic, prognostic and therapeutic agents. view more

The Sfanos Lab studies the cellular and molecular pathology of prostate disease at the Johns Ho...pkins University School of Medicine. We are specifically interested in agents that may lead to chronic inflammation in the prostate, such as bacterial infections and prostatic concretions called corpora amylacea. Our ongoing studies are aimed at understanding the influence of prostate infections and inflammation on prostate disease including prostate cancer and benign prostatic hyperplasia (BPH). The laboratory also focuses on the influence of the microbiome on prostate disease development, progression, and/or resistance to therapy. view more

Prostate cancer is the most commonly diagnosed malignancy in men in the United States, although... our understanding of the molecular basis for this disease remains incomplete. We are interested in characterizing consistent alterations in the structure and expression of the genome of human prostate cancer cells as a means of identifying genes critical in the pathways of prostatic carcinogenesis.

We are focusing on somatic genomic alterations occurring in sporadic prostate cancers, as well as germline variations which confer increases in prostate cancer risk. Both genome wide and candidate gene approaches are being pursued, and cancer associated changes in gene expression analyses of normal and malignant prostate cells are being cataloged as a complementary approach in these efforts.

It is anticipated that this work will assist in providing more effective methodologies to identify men at high risk for this disease, in general, and in particular, to identify new markers of prognostic and therapeutic significance that could lead to more effective management of this common disease. view more

Normal and neoplastic cells respond to genome integrity threats in a variety of different ways.... Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment.

Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens.
Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies.

Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections.
A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer. view more