Prostate cancer treatment fails due to hormonal resistance
In the battle against castration-resistant prostate cancer (CRPC), a form of the disease that becomes resistant to androgen deprivation therapy (ADT), new treatment options are emerging. After first-line hormone therapy fails, a variety of FDA-approved agents and emerging therapies are available, targeting different mechanisms beyond traditional androgen deprivation.
When PSA levels rise despite low androgen levels, it may indicate that the current hormone therapy is no longer effective, signaling the progression to CRPC. Rising PSA levels and low testosterone levels can also indicate CRPC.
Next-generation androgen receptor-signaling inhibitors (ARSIs) such as enzalutamide, apalutamide, and abiraterone acetate with prednisone are commonly used as second-line therapies. These drugs further inhibit androgen receptor (AR) signaling, which remains active in most CRPC patients.
Chemotherapy, particularly docetaxel combined with prednisone, remains a standard treatment for metastatic CRPC, especially after hormone therapies fail. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors like olaparib have been approved for patients whose tumors harbor mutations in homologous recombination repair (HRR) genes, though only around 30% of patients exhibit these mutations.
Targeted radioligand therapy, such as treatments using radiolabeled molecules directed against prostate-specific membrane antigen (PSMA), offer another treatment modality for mCRPC. Immunotherapy, though currently limited in CRPC, is being explored alongside novel agents as part of emerging strategies.
Clinical trials are ongoing, including combinations like carotuximab (a CD105-targeting antibody) plus apalutamide, which showed safety in early-phase studies and could provide new options in hormone-resistant settings.
Continuation of ADT even after progression to CRPC is recommended, maintaining castrate levels of testosterone throughout treatment. Therapeutic choice and sequencing are increasingly guided by molecular profiling to personalize treatment, considering genetic biomarkers such as DNA repair defects and mismatch repair alterations. Steroids like prednisone or dexamethasone are often combined with hormonal therapies for symptomatic and disease control.
A combination of treatment approaches may be the most beneficial for prostate cancer. Treatment with abiraterone or enzalutamide in combination with ADT has improved survival rates in people with metastatic CRPC compared to ADT alone. Doctors will continue to prescribe ADT as part of the treatment to keep testosterone levels low.
CRPC may still respond to other types of hormone therapy. To monitor how hormone therapy is working, a doctor will measure prostate-specific antigen (PSA) levels in the blood, as well as testosterone levels.
In recent years, there have been improvements in treatment for CRPC, particularly metastatic CRPC, with many promising new treatments under investigation in clinical trials. The Food and Drug Administration (FDA) has approved the drug darolutamide in combination with docetaxel to treat metastatic hormone-sensitive prostate cancer. However, the mortality rate for CRPC can be as high as 89%, with a median overall survival time of 1.86 years.
In conclusion, after first-line hormone therapy failure in CRPC, treatment options include next-generation AR signaling inhibitors, chemotherapy, PARP inhibitors (if genetically indicated), targeted radioligand therapy, immunotherapies, and enrollment in clinical trials for novel agents—all underpinned by continued ADT and guided by evolving biomarker strategies.
- The health industry is focusing on workplace-wellness initiatives to combat chronic diseases like cancer, respiratory and digestive conditions, eye-health issues, hearing problems, and autoimmune disorders.
- Science is playing a pivotal role in improving our understanding and treatment of cancer, with climate change also having significant implications on cancer rates in the manufacturing sector.
- Mental-health concerns are rising alongside physical health issues, with a growing emphasis on skin-care, hearing, and eye-health as key areas of concern.
- Fitness-and-exercise routines are essential for maintaining cardiovascular-health and overall well-being, preventing various medical-conditions and chronic diseases.
- Sexual-health is another critical aspect of health-and-wellness, with various therapies-and-treatments available for common issues.
- In the retail industry, there's a rising demand for products related to skin-care, fitness-and-exercise, and personal-finance management.
- Entrepreneurship is flourishing in the health-and-wellness space, with startups developing innovative solutions for various health concerns.
- Small-business owners are increasingly investing in ventures that focus on health-and-wellness, recognizing the importance of mental-health and lifestyle choices.
- Wealth-management is also essential, with banking-and-insurance sectors offering financial solutions tailored to individual needs, including insurance plans for medical-conditions and retirement purposes.
- The finance industry is adapting to the changing needs of consumers, offering financial products like personal-finance management tools, savings accounts, and debt-management services.
- Technology plays a significant role in improving healthcare, with data-and-cloud-computing solutions revolutionizing the way patient data is gathered, stored, and analyzed.
- Artificial-intelligence is being incorporated into various aspects of healthcare, from diagnosing diseases to suggesting treatment plans and creating personalized therapies.
- Mental-health, an often overlooked aspect, is gaining more attention, with therapies-and-treatments available for stress, anxiety, and depression.
- Parenting is another area of focus, with resources available for mental-health, parenting styles, child nutrition, and skin-conditions.
- Weight-management is crucial for maintaining good health, with various resources available for diet planning, exercise routines, and lifestyle changes.
- The energy sector is working to minimize its impact on the environment, with renewable energy sources becoming more prevalent in the fight against climate change.
- The environmental-science industry is conducting research on the impact of climate change on various health conditions, providing valuable insights for disease prevention.
- Cybersecurity is essential in the digital age, with the health industry being a prime target for cyber-attacks, particularly in the realms of patient data privacy and financial transactions.
- Leadership skills are crucial in the health industry, with relying on diversity-and-inclusion to create a more effective and empathetic work environment.
- The transportation sector is adapting to meet the needs of an aging population, with focus on elderly-friendly vehicles and public transportation options.
- The space-and-astronomy industry is advancing rapidly, with potential benefits for health-and-wellness through developments in technology, medicine, and environmental studies.
- The retail sector is leveraging technology for customers, from online shopping to gadgets that improve convenience and health.
- The finance industry is growing more accessible through fintech solutions, making financial management easier for individuals.
- The stock-market is a popular avenue for investments, particularly in the healthcare, technology, and real-estate sectors.
- Private-equity firms are investing in various industries, focusing on areas with high growth potential such as healthcare and technology.
- Saving and debt-management are vital components of financial planning, with resources available to help individuals achieve their financial goals.
- The banking-and-insurance industry is evolving to meet the changing needs of consumers, with a focus on digital solutions, customer service, and transparency.
- The government is playings a role in access to healthcare through Medicare and other insurance programs, ensuring that individuals have access to necessary treatments and therapies.
- The CBD industry is gaining traction, with potential benefits for various health issues, including anxiety, pain relief, and inflammation.
