TY - JOUR. T1 - Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer. AU - Michaelson, M. D.. AU - Bellmunt, J.. AU - Hudes, G. R.. AU - Goel, S.. AU - Lee, R. J.. AU - Kantoff, P. W.. AU - Stein, C. A.. AU - Lardelli, P.. AU - Pardos, I.. AU - Kahatt, C.. AU - Nieto, A.. AU - Cullell-Young, M.. AU - Lewis, N. L.. AU - Smith, M. R.. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Background: This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC). Patients and methods: Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m 2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m 2 (Cohort B1, n = 5) and 1.2 mg/m 2 (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP). Results: Trabectedin ...
TY - JOUR. T1 - Optimal sequencing of new drugs in metastatic castration-resistant prostate cancer. T2 - Dream or reality?. AU - Caffo, Orazio. AU - Lunardi, Andrea. AU - Trentin, Chiara. AU - Maines, Francesca. AU - Veccia, Antonello. AU - Galligioni, Enzo. PY - 2016/9/1. Y1 - 2016/9/1. N2 - The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new ...
BERKELEY, CA (UroToday.com) - Prostate cancer is the most common male cancer in North America. While better screening and treatments have resulted in improved outcomes, a subset of patients eventually develops metastatic disease. Androgen deprivation is highly effective, but eventually resistance develops, leading to a lethal disease phenotype known as metastatic castration-resistant prostate cancer (mCRPC). Traditionally, mCRPC most commonly metastasizes to the bone, and less commonly to other sites. However, coupled with recent regulatory approval of 6 distinctive therapies with different mechanisms of action in the treatment of mCRPC, we have been observing an increasing number of patients now exhibiting disease metastasis at non-osseous sites (e.g., lymph nodes, liver, lung). We thus hypothesize this drug development renaissance has altered the natural history of mCRPC, leading to the emergence of new patterns of metastases.. In our study, we evaluated the pattern of metastatic disease in ...
BERKELEY, CA (UroToday.com) - Prostate cancer is the most common malignancy in men in the United States with an estimated 220 800 new cases and 27 540 deaths in 2015.[1] In 2004, two landmark trials, TAX 327 and SWOG 99-16, revealed an overall survival (OS) benefit in men with progressive metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel,[2, 3] however benefits remain limited. In recent years, agents such as abiraterone and enzalutamide have shown an OS benefit, similar to docetaxel, in the mCRPC population.[4, 5] Several agents that target angiogenesis have been combined with docetaxel in an attempt to improve OS, but unfortunately, the results of these trials have proved to be disappointing. Alternative approaches to targeting tumor vasculature and attempting combination therapies need further investigation. One such alternative approach is targeting CD105, which is involved in normal vascular development, is expressed on proliferating endothelial cells, and has ...
Submission based on PROfound, the first positive Phase III trial testing a targeted treatment in biomarker-selected prostate cancer patients. AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that a supplemental New Drug Application for Lynparza (olaparib) has been accepted and granted Priority Review in the US for patients with metastatic castration-resistant prostate cancer (mCRPC) and deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene mutations, who have progressed following prior treatment with a new hormonal agent.. A Prescription Drug User Fee Act (PDUFA) date is set for the second quarter of 2020.. The Priority Review by the US Food and Drug Administration (FDA) is based on results from the Phase III PROfound trial, which were presented during the Presidential Symposium at the 2019 European Society of Medical Oncology congress.. Results of the PROfound trial showed ...
BACKGROUNDThe neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, has been reported to be a poor prognostic indicator in prostate cancer. Here we explore the use of the NLR to establish a simple prognostic score for men with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel. METHODS: In the training cohort, the NLR and other known prognostic variables were evaluated among a cohort of chemotherapy-naive patients treated with thrice-weekly docetaxel at the Princess Margaret Cancer Centre. Significant prognostic variables identified by univariable Cox regression were evaluated by the area under the receiver operating characteristic curves. Multivariable Cox regression was then used to derive a prognostic score where 1 risk point was assigned for each significant variable. The model was externally validated in a cohort of patients treated at the Royal Marsden. RESULTS: Three hudred fifty-seven patients were analyzed in the training cohort. Median age was 71 ...
Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy. Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n 507) and testing (n 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC). ...
The number of docetaxel cycles completed was associated with improved overall survival among men with metastatic castration-resistant prostate cancer receiving docetaxel, prednisone, and lenalidomide (Revlimid; DPL) or docetaxel/prednisone (DP), in the phase III Mainsail trial. de Morrée et al reported this post hoc analysis in JAMA Oncology.. Study Details. In the Mainsail trial, 1,059 patients were randomized to receive DPL or DP plus placebo until disease progression or unacceptable toxicity. Median overall survival was significantly poorer in the DPL group. Due to greater toxicity, patients in the DPL group received fewer docetaxel cycles (median of 6 vs 8); docetaxel dose intensity was similar in the two groups. In the current analysis, the effect of the number of docetaxel cycles on overall survival was evaluated in the intent-to-treat population.. Association With Survival. On multivariate analysis including all patients, receipt of ≥ 8 cycles of docetaxel was associated with improved ...
Ipilimumab (Yervoy) failed to meet the primary endpoint of improving overall survival in the randomized, phase III CA184-043 trial. However, the immunotherapy did improve progression-free survival and prostate-specific antigen (PSA) response compared with placebo in postdocetaxel metastatic castration-resistant prostate cancer.. Prespecified subset analyses suggested that ipilumumab improves survival in patients with more favorable prognostic factors (ie, no visceral metastasis, lower levels of alkaline phosphatase, and elevated hemoglobin). This finding needs to be validated in future trials.. Immunotherapy Rationale. "Although the primary endpoint of this trial was not met, the antitumor activity [of ipilimumab] is suggested by other efficacy endpoints. It appears that patients with more favorable prognostic factors may be more likely to benefit from ipilimumab treatment. Results of this trial support further investigation of ipilimumab in patients with fewer adverse prognostic features than ...
This study investigated the prostate-specific antigen response and overall survival in patients with metastatic castration-resistant prostate cancer
Therapies for castration‐resistant prostate cancer in a new era: The indication of vintage hormonal therapy, chemotherapy and the new ...
This is an open-label, single arm, two part adaptive design phase II trial of Olaparib in patients with advanced castration resistant prostate cancer.
Estrogens have long played a role in the treatment of advanced prostate cancer, however the mechanism of efficacy in men who have already developed resistance to androgen-deprivation therapies has been uncertain. Estrogens induce feedback inhibition of LH secretion in patients with an intact hypothalamic-pituitary axis, resulting in decreased testosterone production. An early VA Cooperative Urology Group study compared the estrogen diethylstilbestrol (DES) to orchiectomy, and demonstrated that DES provided better cancer specific survival than orchiectomy, but cardiovascular mortality offset the improved disease control [27]. This study raised the possibility that estrogens might inhibit cancer growth independently of simple suppression of testicular androgen production. In support of that idea, our group has previously shown that estradiol inhibits multiple castration resistant human prostate cancer xenografts in castrated animals, however the mechanism remained ambiguous. This study was carried ...
Prostate cancer is the most commonly diagnosed non-cutaneous malignancy of men in the United States and remains the second leading cause of cancer-related mortality among men. Novel approaches are necessary to personalize and improve treatment. The androgen receptor (AR) plays a critical role in the normal development and function of the prostate and promotes growth in most prostate cancers. Most patients with advanced prostate cancer have cancer that will initially respond to androgen-targeting therapy (focusing on decreasing the circulating levels of testosterone which is the primary source of ligand for the AR receptor). However, castrate resistance usually develops within 18 to 24 months and the median survival of men with castration resistant prostate cancer (CRPC) ranges between 12 to 18 months. Current options are limited including: secondary hormonal manipulations, radiopharmaceuticals, and chemotherapy and only docetaxel, a taxane that targets microtubules, has been proven to prolong ...
2016 Society for Endocrinology. Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct ...
TY - JOUR. T1 - Sequencing Treatment for Castration-Resistant Prostate Cancer. AU - Handy, Catherine E.. AU - Antonarakis, Emmanuel. PY - 2016/12/1. Y1 - 2016/12/1. N2 - Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node. Those with asymptomatic bone-only disease could be considered for sipuleucel-T, abiraterone, enzalutamide, or docetaxel in the first-line setting. For symptomatic disease, docetaxel ...
[151 Pages Report] Check for Discount on Global Castration-Resistant Prostate Cancer Therapeutics Consumption 2016 Market Research Report report by QYResearch Group. The Global Castration-Resistant Prostate Cancer Therapeutics Consumption 2016 Market...
Dear Dr. Reed, Some concerns about male to female hormone therapy. Following your reply to a few questions here, I am planning to call your office tomorrow to arrange for orchiectomy in early April of 2017. I am impressed with your work as I have viewed your website srsMiami.com I am in very good health and meet the requirements you have posted to me. You were recommended from my therapist from Miami. I trust her judgement and expertise. So I have two concerns. While being convinced that you are a qualified person to do my SRS. However, financial constraints at this time would permit only bilateral orchiectomy. Your fee is 2500.00 You sent me information on SRS but I did not get anything about Orchiectomy. Hormones have been working very good for me and I have been feeling good. However my doctor suggested lowering my spironolactone to avoid unnecessary risks to my health. My question is whether I have to stop hormone therapy for the orchiectomy procedure. Is there a certain dosage that is ...
Dr. Shore presented on the relationship between quality of live and overall survival in metastatic castrate-resistant prostate cancer patients with Radium-223 administration analyzed by prior docetaxel. Using the functional assessment of cancer therapy-prostate (FACT-P) they were able to create a time dependent model for change in health-related quality of life scores.
The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.
This trial is investigating the efficacy of buparlisib with cabazitaxel in patients with metastatic castration resistant prostate cancer previous treated with
@vasregret inspired me to do a similar post for my Bilateral orchiectomy. As has been previously discussed- so far so good. No regrets. I decided to go bilateral in one operation, despite advice to do one at a time, unde…
@vasregret inspired me to do a similar post for my Bilateral orchiectomy. As has been previously discussed- so far so good. No regrets. I decided to go bilateral in one operation, despite advice to do one at a time, unde…
Excerpt:. "In the phase III CA184-095trial reported in the Journal of Clinical Oncology, Tomasz M. Beer, MD, FACP, of the Knight Cancer Institute, Oregon Health and Science University, and colleagues found that ipilimumab (Yervoy) did not increase overall survival vs placebo in men with asymptomatic or minimally symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Ipilimumab was associated with prolonged progression-free survival and a higher prostate-specific antigen (PSA) response rate.". Go to full article.. If youre wondering whether this story applies to your own cancer case or a loved ones, we invite you to use our ASK Cancer Commons service.. ...
References. 1. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration- Resistant Prostate Cancer. Eur Urol. 2014;65:467-79.. 2. Cookson MS, Roth BJ, Dahm P, Engstrom C, Freedland SJ, Hussain M, et al. Castration-resistant prostate cancer: AUA guideline. 2013.. 3. NCCN. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. 2014.. 4. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983-92.. 5. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138-48.. 6. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, ...
OBJECTIVE: The purpose of this study was to compare the effects of castration on cell death rate of the adult rat prostates and to evaluate the benefic action of alpha tocopherol supplementation to avoid apoptosis post-orchiectomy. MATERIAL AND METHODS: Thirty male Wistar rats weighing 250-300g were divided into three groups: group I - they were subjected to bilateral orchiectomy and sacrificed eight weeks after the procedure; group II - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure; and group III - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards ...
79 NCCN Guidelines for Patients ® Prostate Cancer, Version 1.2016 7 Treatment guide: Systemic treatment Castration-naïve prostate cancer Guide 19 lists options for advanced cancer that has never been treated with castration methods. Options are grouped by whether the cancer is staged M0 or M1. Orchiectomy When talking about prostate cancer, castration is a term that means the testicles are making little or no testosterone. It can be achieved by an operation or by medicines. Surgical castration that removes both testes is called a bilateral orchiectomy. This surgery is a type of ADT. Orchiectomy is a treatment option for both M0 and M1 cancers. LHRH agonist and antagonist Medical castration works equally as well as surgical castration. Medicines used to cause castration include an LHRH antagonist or agonist. They are a type of ADT. As discussed next, an antiandrogen may be added. The risk for side effects can be reduced by intermittent use of your medicine. Intermittent treatment improves ...
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole-genome RNA sequencing, gene set enrichment analysis, and immunohistochemistry. Our analyses revealed 5 mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: AR-high tumors (ARPC), AR-low tumors (ARLPC), amphicrine tumors composed of cells coexpressing AR and NE genes (AMPC), double-negative tumors (i.e., AR-/NE-; DNPC), and tumors with small cell or NE gene expression without AR activity (SCNPC). RE1 silencing transcription factor (REST) activity, which suppresses NE gene expression, was lost in AMPC and SCNPC PDX models. However, knockdown of REST in cell lines revealed that attenuated REST activity drives the AMPC phenotype but is not sufficient for ...
Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment ...
The frequency of traditional CTCs, CTC Clusters, small CTCs, CK- CTCs, and high nuclear & cytoplasmic AR CTCs increased by line of therapy and increasing disease burden. The increased ratio of non-traditional to traditional CTCs with lines of tx may indicate an evolved, more resistant disease due to increased tx exposure. Increased CTC heterogeneity within and between pts suggests multiple mechanisms of resistance including constitutively active AR signaling, AR signaling independence, and epithelial plasticity. A relationship to disease burden cannot be excluded. This heterogeneity may explain the specific response to new therapies in the post AA + P & E mCRPC. ...
OncologyPRO is the home of ESMOs educational & scientific resources, with exclusive content for ESMO members such as ESMOs Congresses webcasts,
Dr. Reed, I am ready to schedule in for an Orchiectomy in Miami. I am 35 and have my letters, and medically in good shape.. Nora. Dear Nora,. Thank you for visiting our web-site srsmiami.com/orchiectomy Do Email me at reed (at) srsMiami (dot) com and I will send you a packet of information. Orchiectomy is virtually painless as we use IV sedation, numbing cream, followed by local anesthesia. As you may know we work through a singular small vertical midline incision and yes we remove the spermatic cords (tootsie rolls) as well.. Plan on staying at the Daddy O hotel one block away for 2 post operative days to minimize bruising and discomfort.. Talk with you soon.. Harold M. Reed, M.D ...
American Health & Drug Benefits® examines drug and other healthcare intervention value from the separate and unified vantage points of each stakeholder group to the process: payers, purchasers, providers, patients, manufacturers, regulators, distributors, and evaluators. Directly or indirectly, all parties to healthcare benefits influence policy and demand satisfaction of their interests.
Surgical castration via orchiectomy for metastatic prostate cancer is associated with lower risks for adverse effects compared with medical castration via GnRHa therapy.
Castration-resistant prostate cancer is the metastatic state of prostate cancer which occurs in 90% of the prostate cancer patients and thus reducing the s
Bayer HealthCare and Orion Corporation, a pharmaceutical company based in Espoo, Finland, have begun to enroll patients in a Phase III trial with ODM-201, an investigational novel oral androgen receptor (AR) inhibitor in clinical development for the treatment of patients with prostate cancer. The study, called ARAMIS, evaluates ODM-201 in men with castration-resistant prostate cancer […]. ...
... Prostate Cancer and Prostatic Diseases advance online publication, January 28 2014. doi:10.1038/pcan.2013.62 Authors: J R Gsponer, M Braun, V J Scheble, T Zellweger, A Bachmann, S Perner, T Vlajnic, M Srivastava, S-H Tan, A Dobi, I A Sesterhenn, S Srivastava, L Bubendorf &C Ruiz...
SPARTAN: A Study of Apalutamide (ARN-509) in Men with Non-Metastatic Castration-resistant Prostate Cancer - Alan Bryce, MD. and E. David Crawford, MD.
The article entitled, "The Impact of Surgical Castration on Sexual Recidivism Risk Among Sexually Violent Predatory Offenders," which appears in this edition of the Journal, takes up several important subjects of both a psychiatric and a forensic nature.1 There are two fundamental questions: first, what does the scientific evidence have to say about the likely impact of surgical castration on sexual drive and the enactment of sexually motivated behavior-most specifically, sexual behavior that is criminal in nature? Second, how heavily should the impact of a testosterone-lowering intervention, such as surgical castration, be weighted when attempting to determine the likely risk of future sexual recidivism by a previously civilly committed sexual offender who is seeking possible release into the community? It should be emphasized that the authors have conducted a retrospective review that attempts to predict the possible effects of surgical castration on civilly committed sexual offenders, rather ...
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended darolutamide, an androgen receptor inhibitor (ARi), for marketing authorization in the European Union (EU).. The compound, which is developed jointly by Orion Corporation and Bayer, is recommended for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The final decision of the European Commission on the marketing authorisation is expected in the coming months. The androgen receptor inhibitor (ARi) is already approved in the in the U.S., Brazil and Japan and filings in other regions are underway or planned by Bayer.. Bayer is responsible for global commercialization of darolutamide, with a co-promotion of Bayer and Orion in certain European markets, e.g. in France, Germany, Italy, Spain, the UK, Scandinavia and Finland.. The CHMP recommendation is based on the results of the Phase III ARAMIS ...
Prolonged event-free survival achieved with orteronel as switch maintenance therapy in patients with non-progressive disease following chemotherapy
RODERIC (Repositori dObjectes Digitals per a lEnsenyament la Recerca i la Cultura) es el repositorio institucional de la Universitat de València. Se concibe como una ventanilla única para el acceso y la difusión de la producción digital de la Universitat. RODERIC responde al compromiso de la Universitat con el movimiento de acceso abierto al conocimiento adquirido con su adhesión a la Declaración de Berlín (30 Septiembre de 2008).
Adding Xtandi to hormone therapy reduces the risk of metastasis in castration-resistant prostate cancer patients, new data from a Phase 3 trial shows.
Purpose: In addition to their expression on pituitary cells, receptors for luteinizing hormone-releasing hormone (LH-RH) are found on most prostate cancer cells. These tumoral LH-RH receptors mediate the direct cytotoxic effects of LH-RH analogs and are potential therapeutic targets. Although pituitary LH-RH receptors are downregulated following prolonged exposure to LH-RH agonists, there is no evidence that tumoral receptors behave in a similar manner. To better characterize expression of tumoral LH-RH receptors, specimens of prostate cancer from various cohorts of patients were analyzed.. Experimental Design: Surgical specimens were obtained from untreated patients with prostate cancer and from patients with metastatic castration-resistant prostate cancer previously treated with bilateral orchiectomy. To address the possibility of receptor downregulation, two additional cohorts of patients who had been previously treated with LH-RH agonists were included. One group received neoadjuvant therapy ...
What is castration?. Castration is the act of removing an individuals use of the testicles by means of surgery or the use of chemicals. Surgical castration is bilateral orchiectomy (excision of both testes), and chemical castration uses pharmaceutical drugs to deactivate the testes. Castration causes sterilization (preventing them from reproducing); it also greatly reduces the production of certain hormones, such as testosterone.. Types of castration. There are two types of approaches to castration. That is, chemical and surgical.. ...
In this study, we provide in vivo preclinical evidence from a refined GEM model of CRPC, complemented by analyses of human prostate cancer cells in culture, to show the efficacy of dual targeting of Akt/mTOR signaling for treatment of CRPC. An important feature of our refined GEM model is that tumors arise following inducible Pten inactivation in the adult prostate, which differs from previous GEM models on the basis of conditional inactivation of Pten in immature prostate epithelium, or its germline loss-of-function (34, 36, 38). Nonetheless, in this new GEM model, as was the case for the previous ones (34, 36), castration results in an initial regression, followed by the emergence of castration-resistant tumors that are more aggressive than their noncastrated counterparts. Importantly, our findings indicate that these castration-resistant tumors, which are otherwise quite similar to their noncastrated counterparts, display a virtual absence of senescence, which is a hallmark of Pten ...
CHICAGO -- The addition of bevacizumab (Avastin) to chemotherapy in treating metastatic castrate-resistant prostate cancer patients fell short of providing a survival benefit to patients, researchers
Many patients with prostate cancer develop resistance to androgen-deprivation therapy and progress to an aggressive castration-resistant prostate cancer (CRPC). These patients have a poor prognosis and often have activation of androgen receptor (AR) signaling via alternative pathways, but the mechanisms underlying castration resistance remain poorly understood. Calcinotto and colleagues sought to understand the role of the tumor microenvironment in CRPC progression. Analysis of biopsies from patients with CRPC compared with castration-sensitive prostate cancer (CSPC) revealed that CRPCs had an enrichment of poly-morphonuclear myeloid-derived suppressor cells (PMN-MDSC). In mouse models of CRPC, PMN-MDSC infiltration was linked to AR activation, and thereby conferred castration resistance. Treatment with a CXCR2 antagonist reduced PMN-MDSC infiltration and delayed the progression to CRPC. Tumor-infiltrating MDSCs secreted IL23, which induced transcription of AR target genes, conferred resistance ...
The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in
In their study, Rivera-Arkoncel and her colleagues compared 38 men with prostate cancer who received ADT and 36 men with less advanced prostate cancer who did not receive hormonal therapy. Men in the ADT group either underwent bilateral orchiectomy at least six months earlier or received six or more months of treatment with injections of GnRH agonists. Both groups received treatment at the Philippine General Hospital from 2004 to 2010. Although the average age of the two groups was not the same at the beginning of the study, the groups were similar in terms of other diabetes risk factors, Rivera-Arkoncel said ...