Analysis Of Clinical Trials In Mainland China
The clinical investigations on the use of therapeutic drugs for PC in mainland China and worldwide were compared. In mainland China, 31 trials were completed in the last 10 years, including 21 on endocrine therapy, six on chemotherapy, three on radiotherapy, and one on immunotherapy. Most of these trials were phase III or phase IV trials , whereas only 12 were phase I or II trials . The therapeutic targets in each of these trials were identified . Endocrine therapy targets included androgen receptor , gonadotropin-releasing hormone , and cytochrome p450c17 . Chemotherapy targets included microtubules , poly polymerase , PKC , and S100A9 . All three radiotherapy trials used radium-223 to target actively dividing cancer cells . The single immunotherapy trial was a T-cell therapy targeting NY-ESO-1. China differs from other regions of the world in that drug targets in mainland Chinainitiated trials are limited. Moreover, the number of organizations conducting clinical trials on PC therapies is relatively low these trials were mainly done in large cities such as Shanghai, Beijing, Guangzhou, and Chengdu .
Figure 3 Prostate cancer therapy trial classification and geographical locations. Therapy type and targets for PC in clinical trials in mainland China. Cities with organizations for PC drug clinical trials .
Classification Of Drugs In Clinical Investigations
Globally, 132 different drugs were used for treating PC in all completed trials, including 25 endocrine therapy, 59 chemotherapy, 6 radiotherapy, and 42 immunotherapy . Trials investigating 19 drugs targeting PC were completed in mainland China in the last 10 years, including 12 for endocrine therapy, 5 for chemotherapy, 1 for radiotherapy, and 1 for immunotherapy . The treatments for PC evaluated in trials over the past 10 years were predominantly chemotherapeutic worldwide, whereas endocrine therapy was the dominant therapy in China.
Figure 2 Classification of drugs in clinical trials for prostate cancer worldwide and in mainland China .
Followup By Primary Care Physicians
The American Cancer Society has released evidence- and expert-based guidelines for the management of prostate cancer survivors by primary care physicians , a response to the fact that as the number of men surviving prostate cancer has increased, reliance on PCPs for their care has grown as well. The guidelines address promotion of healthy lifestyles, surveillance for disease recurrence, screening for second primary cancers, and evaluation and management of adverse physical and psychosocial effects caused by the disease and its treatment. Recommendations include the following :
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Drug Developed In Part By Musc Holds Promise For Treating Advanced Prostate Cancer
With a goal of improving survival for men with metastatic prostate cancer, researchers from MUSC Hollings Cancer Center are testing a new drug that may help to expand treatment options for patients whose disease is progressing despite treatment with standard therapies. The study will also examine patients genetic profiles for clues as to which men may be more responsive to the new therapy.
The investigational drug, called opaganib, is no stranger to Hollings researchers, as it was developed in part at the Medical University of South Carolina through the work of Charles Smith, Ph.D., and Besim Ogretmen, Ph.D. The first human trial was also conducted at MUSC, with the results showing that the drug was well-tolerated and provided some clinical benefit.
Opaganib works by selectively targeting an enzyme that regulates the balance between two types of lipids in the body: one that is more likely to help the cancer to grow and spread, and one that is more likely to cause the cancer cells to die. As far as the researchers know, the drug is the only one in development that can shift this balance to create more of the lipids that help to kill the cancer cells.
Because of the way it works, opaganib may provide benefit in multiple cancer types and has already been tested in both gallbladder cancer and multiple myeloma. The drug is also currently being tested as a potential treatment for patients with severe COVID-19-related pneumonia.
Trends Of Clinical Trials On Pc Therapy Over Time
From January 1, 2010 to January 1, 2020, 1041 clinical trials testing 230 PC drugs were carried out worldwide. The total number of trials worldwide has not much changed over the past 10 years with an average annual growth rate of 2.5% . However, China represents an increasing percentage of the total trials, especially after 2017, with an average annual growth rate of 29.8%.
Figure 1 Trends of clinical trials of prostate cancer therapy in China and worldwide. Left y-axis indicates the ratio of total trials, and right y-axis indicates the total number of trials.
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Adc Development For Prostate Cancer
Prostate cancer is one of the most common cancers in men. The standard treatment for patients with metastatic castration-resistant prostate cancer have been assessed but failed to improve the overall survival . Currently, novel treatment methods such as the targeted antibody-drug conjugates have been found to significantly improve the progression-free survival and OS rates.
Creative Biolabs offers high-quality services in the ADCs discovery and development against mutiple cancers. With a lot of talent scientists and technicians, we have built excellent and mature platforms for the development and manufacturing of ADCs. In addition, we will also save your time and cost by taking advantage of our expertise and innovative bio-conjugation and analysis technology.
Rational Drug Discovery In Progress
A growing amount of evidence suggests that mutations in the AR-encoding gene occur spontaneously in prostate cancer and eventually result in the relapse of patients. As a consequence, the effects of drugs change, and patients are no longer responsive to treatment. These gain-of-function mutations present a scientific challenge to pharmacologically overcome the mechanisms of drug resistance and further highlight the importance of identifying advanced compounds to inhibit AR activity. Rational drug design, which is the application of a structure-function relationship, is now widely used in modern medicinal chemistry for developing exquisitely selective ligands.
Can the available structural information on AR-ligand interactions based on x-ray crystallography and modeling be exploited for the rational design of next-generation antiandrogens to overcome problems with antiandrogen resistance? Available structures of the wild-type and mutant AR in complex with ligands reveal a clear explanation for how changes in a single residue can result in dramatic changes in ligand-binding properties and pinpoint the key determinants of receptor-ligand specificity and affinity. This information will greatly facilitate the development of new antagonists for the treatment of prostate cancer. Hence, this section will provide an overview of the development of new antiandrogens.
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Introduction Of Prostate Cancer
Prostate cancer is cancer that arises in the prostate, a small walnut-shaped gland in the male reproductive system to produce the seminal fluid. In general, most prostate cancer grows slowly and limitedly in the prostate gland. While some of the cancer are aggressive and can spread quickly to other organs especially the bones and lymph nodes. Symptoms during the cancer mainly show difficulty urinating, decreased force in the stream of urine, blood in semen, discomfort in the pelvic area, bone pain and erectile dysfunction. Although the specific cause of prostate is unclear, some risk factors may include age, race, family history and obesity. Besides, the cancer often leads to some complications such as the metastasis and incontinence. The treatment options for this cancer include surgery to remove the prostate, radiation therapy, hormone therapy, chemotherapy and biological therapy.
Fig.1 Metastatic properties of prostate cancer.
Adverse Effects Of Androgen Suppression
Surgical and medical castration lead to a number of adverse effects, including the following, that can have a significant impact on a mans quality of life:
- Psychological changes
- Weight gain
In addition, in men with prostate cancer receiving ADT, lean body mass decreases significantly after 12-36 months of treatment.
Uncertainty remains about the impact of androgen ablation on cardiovascular morbidity and mortality. However, the combination of weight gain and anemia in men with asymptomatic cardiovascular disease could adversely affect survival in some cases.
The FDA has advised that manufacturers of gonadotropin-releasing hormone agonists, which are approved for palliative treatment of advanced prostate cancer, must add safety warnings about the increased risk of diabetes and certain cardiovascular diseases in men receiving these medications. The FDA notes that although the risk for these complications appears to be low, physicians should evaluate patients for risk factors for these diseases before prescribing these agents.
Patients receiving GnRH agonists should be actively monitored for diabetes and cardiovascular disease and treated when possible. Periodic measurement of fasting glucose, cholesterol, triglycerides, and blood counts should be performed. In addition, the package inserts for all LHRH medications recommend periodically measuring serum testosterone, because levels above 50 ng/dL do occur and may adversely affect long-term survival.
Acute kidney injury
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Bone Protection In Patients Receiving Androgen Blockade
Two drugs, the bisphosphonate zoledronic acid and the RANKL inhibitor denosumab, have been approved to treat osteoporosis secondary to androgen deprivation. Zoledronic acid is administered as an intravenous infusion. Denosumab is administered subcutaneously. These drugs are given along with supplemental vitamin D and calcium. Patients should be monitored regularly for hypocalcemia. Both agents are associated with a low incidence of osteonecrosis of the jaw. Both drugs delay the risk of skeletally-related events by relieving bone pain, preventing fractures, decreasing the need for surgery and radiation to the bones, and lowering the risk of spinal cord compression.
A double-blind, placebo-controlled, multicenter study in men with primary or hypogonadism-associated osteoporosis found that over a 14-month period, treatment with zoledronic acid reduced the risk of vertebral fractures by 67%. New morphometric vertebral fracture occurred in 1.6% of men taking zoledronic acid and in 4.9% taking placebo. Patients receiving zoledronic acid had significantly higher bone mineral density and lower bone-turnover markers. However, the rate of myocardial infarction was higher in the treatment group .
Improving The Odds Of Success In Prostate Cancer Therapy Development
In recognition of Mens Health Month, Parexel offers a deep dive into the challenges of developing therapies for prostate cancer. Despite significant research advances, prostate cancer remains the second most frequently diagnosed cancer and the sixth most common cause of death from cancer among men worldwide.
Prostate cancer treatments have evolved over the 15 years since the release of docetaxel. Treatment teams are now multi-disciplinaryin addition to just urologists, today medical and radiation oncologists, and a host of support personnel work to provide hope to patients. An increasing number of diverse agents, including chemotherapy drugs, anti-androgens, radiopharmaceuticals, and immune therapies benefit patients.
Despite these advances, the number of available treatment options for prostate cancer patients pales in comparison to those for patients with breast or lung cancer, producing a substantial unmet need.
The potential for further prostate cancer research advances is exciting. On the other hand, small to mid-size biotech companies looking to make an impact in this area face steep competition. Developing a strong understanding of the environmentboth approved products and those in the development pipelineand the diseases natural history are key prerequisites for success.
Fig. 1: After languishing for decades, the development of prostate cancer drugs accelerated rapidly in the last 15 years, resulting in an array of new products to treat late-stage disease.
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Prostate Cancer Treatment Moving Toward Personalized Approach With 6 New Drugs In The Pipeline
Although options for prostate cancer have historically been limited, the late-stage prostate cancer pipeline holds promise for the future of this second most common cancer among men, according to GlobalData a leading data and analytics company.
GlobalData predicts the launch of 12 new agents among the eight major markets* , covering eight mechanisms of action , six of which will be brand new to this market. Novel MOAs for prostate cancer include Poly polymerase inhibitors, one Akt inhibitor, one radioligand, and checkpoint inhibitors.
Heather Leach, Director of Oncology and Hematology at GlobalData, commented Among the most significant developments is the promise for precision medicine within this indication. Although other cancers have benefited from the incorporation of predictive biomarkers into the treatment paradigm, such as in breast cancer or non-small cell lung cancer, prostate cancer has lagged in this area.
However, there are six new therapies that hold potential to change this, including all four PARP inhibitors, ipatasertib , and 177Lu-PSMA-617 , which are in development for patients with homologous recombination deficiencies , phosphatase and tensin homolog loss, and prostate-specific membrane antigen expression, respectively.
Leach concludes Between these agents, GlobalData expects that nearly all prostate cancer cases will hold a biomarker amenable to treatment with at least one of these agents.
* US, France, Germany, Italy, Spain, UK, Japan, and China)
Compounds Targeting Androgen Signaling
The rising PSA levels measured in prostate cancer patients who become resistant to ADT indicate that AR signaling remains an essential target for pharmacological intervention at this stage. This vulnerability is addressed with steroid synthesis inhibitors and with second-generation AR antagonists . Selected phase 3 clinical studies with drugs targeting the AR pathway are listed in .
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Prostate Cancer Clinical Trials Consortium
The Prostate Cancer Clinical Trials Consortium is a clinical research group sponsored by the Prostate Cancer Foundation and the Department of Defense Prostate Cancer Research Program , with its Coordinating Center headquartered at Memorial Sloan Kettering Cancer Center. The PCCTC is currently composed of 11 participating clinical research sites and 32 affiliated clinical research sites.
Visit the PCCTC site for trial information: www.pcctc.org
What Can We Do For You
Scientists at Creative Biolabs are experts in antibody/protein development and antibody/protein-drug conjugation. At present, we provide a full range of ADCs design and construction services against prostate cancer. Our best-quality services include specific antibody development, potent drug or linker-payload production and effective bio-conjugation with unbeatable rapid turnaround times. Targets of ADC development for prostate cancer:
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Prostate Cancer Emerging Drugs Chapters
This segment of the Prostate Cancer report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.
Prostate Cancer Emerging Drugs
Pembrolizumab: Merck & Co
Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Currently, it is in phase 3 stage of development to treat Prostate Cancer.
ZEN 3694: Zenith Epigenetics
The companys lead product, ZEN-3694, a BET inhibitor, in combination with enzalutamide, is in a Phase 2 randomized clinical trial for treatment of metastatic castration resistant Prostate Cancer in patients that have progressed on an androgen receptor signaling inhibitor.
EPI-7386: ESSA Pharma
Early Versus Delayed Treatment
In the years following the introduction by Huggins and Hodges of hormone therapy for prostate cancer, early institution of such treatment was recommended, based on comparison with historical controls. Later, the Veterans Administration Cooperative Urology Research Group studies resulted in the recommendation to defer hormone therapy until symptomatic progression occurred this was thought to avoid the promotion of early androgen resistance in prostate tumors.
Subsequently, the controversy of the appropriate timing of ADT was renewed because of the advent of an LHRH antagonist and LHRH agonists. Laboratory studies demonstrated that early hormone therapy does not confer early resistance. Moreover, clinical trials found that it provided significantly longer survival with fewer complications than did deferred treatment.
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Bet Inhibition In Treatment Of Mcrpc
A company called Zenith Epigenetics has recently reported data from a Phase I/II clinical trial of a drug known as ZEN003604 or ZEN-3694 in the treatment of men with metastatic, castration-resistant prostate cancer who have progressed on treatment with either abiraterone + prednisone or enzlautamide . READ MORE
Prostate Cancer: Therapeutic Assessment
This segment of the report provides insights about the different Prostate Cancer drugs segregated based on following parameters that define the scope of the report, such as:
- Major Players in Prostate Cancer
There are approx. 200+ key companies which are developing the therapies for Prostate Cancer. The companies which have their Prostate Cancer drug candidates in the most advanced stage, i.e. phase III include, Merck & Co.
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Study Of Pembrolizumab Plus Docetaxel Versus Placebo Plus Docetaxel In Chemotherapy
Merck is conducting this clinical trial to find out if the investigational medication pembrolizumab in combination with docetaxel and prednisone is safe and works to slow down or stop the growth of metastatic Castrate Resistant Prostate Cancer compared to docetaxel and prednisone alone. Pembrolizumab is a type of immunotherapy, which may help the bodys immune system attack cancer cells. To be eligible for this trial, patients with mCRPC must not have received chemotherapy for mCRPC and have received prior treatment with either abiraterone acetate or enzalutamide . Additional eligibility criteria will apply. Click here to learn more about this trial on the sponsors website.
To learn more about this study and to find out if you may be eligible, please visit:
ClinicalTrials.gov Identifier: NCT03834506
Early Evidence Regarding Combinations Of Parp Inhibitors With Standard Mcrpc Therapies
There is conflicting evidence supporting the use of PARP inhibitors in mCRPC patients without mutations in DNA repair genes. The potential utility of PARP inhibitors in this setting will likely only be in combination with another effective agent. Preclinical studies have shown that inhibiting the androgen pathway can induce cell sensitivity to PARP inhibition, suggesting a synergy between androgen pathway blockade and PARP inhibitorsforming the hypothesis of multiple clinical trials . Ongoing phase 2/3 controlled clinical trials investigating PARP inhibitors in mCRPC with or without the concurrent administration of another agent have been summarized .
Table 1 Ongoing phase 2/3 controlled trials investigating PARP inhibitors in mCRPC
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