Samuel Denmeade

Last updated

Samuel Ray Denmeade is a Professor of Oncology, Urology and Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine. [1] Over 10 of his published papers have each been cited over 100 times. [2]

As a clinical oncologist Denmeade has been the lead investigator on clinical trials testing new hormone therapies for prostate cancer [3] and is also a laboratory scientist focused on the development of novel ways to treat prostate cancer.[ citation needed ] His main research focus has been on the design and characterization of prodrugs and protoxins targeted for activation by cancer specific proteases. [4] [5] This research is based on the strategy that lethal drugs/toxins could be disguised as a prodrug and only released when exposed to the enzymatic activity of proteases such as PSA which are only present in its enzymatically active form in the tumor and not elsewhere in the body[ citation needed ]. One of these prodrugs termed G202 consists of an analog of the highly toxic natural product thapsigargin coupled to a peptide recognized as a substrate by the protease Prostate-Specific Membrane Antigen. [6] The G202 prodrug is currently being evaluated for its toxicity and therapeutic effectiveness in clinical trials sponsored by GenSpera, Inc.

Denmeade is a co-founder of GenSpera and serves as its Chief Medical Advisor. He is also one of the co-inventors of PRX302 , a modified form of the potent bacterial toxin proaerolysin reengineered for activation by the protease prostate-specific antigen (PSA). PRX302 is currently under clinical development by Protox (now Sophiris), Inc. as therapy for benign prostatic hyperplasia and prostate cancer. [7]

Related Research Articles

Prostate gland of the male reproductive system in most mammals

The prostate is an exocrine gland of the male reproductive system in most mammals and some invertebrates. It differs considerably among species anatomically, chemically, and physiologically. The word prostate comes from Ancient Greek προστάτης, prostátēs, literally "one who stands before", "protector", "guardian".

Prostate cancer male reproductive cancer

Prostate cancer is the development of cancer in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, some grow relatively quickly. The cancer cells may spread from the prostate to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, it can lead to difficulty urinating, blood in the urine or pain in the pelvis, back, or when urinating. A disease known as benign prostatic hyperplasia may produce similar symptoms. Other late symptoms may include feeling tired due to low levels of red blood cells.

Benign prostatic hyperplasia noncancerous increase in size of the prostate

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.

Prostate-specific antigen mammalian protein found in Homo sapiens

Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland.

Chimeric antigen receptor T cells are T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy.

Cancer immunotherapy Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy is the artificial stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspeciality of oncology.

Prostate cancer staging is the process by which physicians categorize the risk of cancer having spread beyond the prostate, or equivalently, the probability of being cured with local therapies such as surgery or radiation. Once patients are placed in prognostic categories, this information can contribute to the selection of an optimal approach to treatment. Prostate cancer stage can be assessed by either clinical or pathological staging methods. Clinical staging usually occurs before the first treatment and tumour presence is determined through imaging and rectal examination, while pathological staging is done after treatment once a biopsy is performed or the prostate is removed by looking at the cell types within the sample.

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates.

Glutamate carboxypeptidase II mammalian protein found in Homo sapiens

Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

Saw palmetto extract is an extract of the fruit of the saw palmetto. It is marketed as a treatment for benign prostatic hyperplasia (BPH), but reviews of clinical trials, including those conducted by the National Center for Complementary and Alternative Medicine, found it ineffective for this purpose.

Northwest Biotherapeutics is a development-stage American pharmaceutical company headquartered in Maryland that focuses on developing immunotherapies against different types of cancer. It was founded in 1996 by Alton L. Boynton.

Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. Although LUTS is a preferred term for prostatism, and is more commonly applied to men, lower urinary tract symptoms also affect women.

Prostate cancer antigen 3 is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy - including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination.. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance.. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

GenSpera

Inspyr Therapeutics, Inc. is a development-stage pharmaceutical company based in San Antonio, Texas. The company is focused on therapeutics that deliver a cancer-destroying drug directly to the tumor or its supporting environment, the tumor vasculature.

Directed enzyme prodrug therapy (DEPT) uses enzymes artificially introduced into the body to convert prodrugs, which have no or poor biologically activity, to the active form in the desired location within the body. Many chemotherapy drugs for cancer lack tumour specificity and the doses required to reach therapeutic levels in the tumour are often toxic to other tissues. DEPT strategies are an experimental method of reducing the systemic toxicity of a drug, by achieving high levels of the active drug only at the desired site. This article describes the variations of DEPT technology.

PROSTVAC is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of all prostate cancer although clinical trials are focusing on more advanced cases of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is a vaccine designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell immune response to cancer cells that express the tumor-associated antigen prostate-specific antigen (PSA).

Kevin M. Slawin is an American physician and the founder of Bellicum Pharmaceuticals and the Vanguard Urologic Institute at Memorial Hermann Medical Group. He was also the Director of Urology at Memorial Hermann Hospital. Slawin specializes in the diagnosis and treatment of urologic cancers and robotic surgery. He is also possesses patents related to the advancement of prostate cancer diagnosis, staging and treatment and to the cellular immunotherapy of cancer.

Ralaniten acetate chemical compound

Ralaniten acetate is a first-in-class antiandrogen that targets the N-terminal domain (NTD) of the androgen receptor (AR) developed by ESSA Pharmaceuticals and was under investigation for the treatment of prostate cancer. This mechanism of action is believed to allow the drug to block signaling from the AR and its splice variants. EPI-506 is a derivative of bisphenol A and a prodrug of ralaniten (EPI-002), one of the four stereoisomers of EPI-001, and was developed as a successor of EPI-001. The drug reached phase I/II prior to the discontinuation of its development. It showed signs of efficacy in the form of prostatic specific antigen (PSA) decreases (4–29%) predominantly at higher doses (≥1,280 mg) in some patients but also caused side effects and was discontinued by its developer in favor of next-generation AR NTD inhibitors with improved potency and tolerability.

Steroidal antiandrogen

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.

References

  1. "Prostate cancer testosterone". jhu.edu. Retrieved November 16, 2017.
  2. "Samuel Denmeade" . Retrieved November 16, 2017.
  3. "Winning the Prostate Cancer War". menshealth.com. April 26, 2017. Retrieved November 16, 2017.
  4. "Samuel Denmeade". pcf.org. Retrieved November 16, 2017.
  5. "Strategy Might Thwart Resistance to a Common Prostate Cancer Treatment". healthday.com. January 7, 2015. Retrieved November 16, 2017.
  6. Denmeade S, Mhaka AM, Rosen DM, Brennen WN, Dalrymple S, Dach I, Olesen C, Gurel B, Demarzo AM, Wilding G, Carducci MA, Dionne CA, Møller JV, Nissen P, Christensen SB, Isaacs JT (2012). "Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy". Science Translational Medicine. 4 (140): 140ra86. doi:10.1126/scitranslmed.3003886. PMC   3715055 . PMID   22745436.
  7. Denmeade, Samuel; Egerdie B; Steinhoff G; Merchant R; Abi-Habib R; Pommerville P. (2011). "Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia". European Journal of Urology. 59 (5): 747–754. doi:10.1016/j.eururo.2010.11.024. PMC   3454506 . PMID   21129846.