Hello fellow warriors, Is there any other warriors that are still hormone sensitive and taking darolutamide?
Are there any HSPC taking it without docetaxel.
Trying to find data on length before drug failure?
I have been on it for 6 months now.
I have been interested in early detection strategies for resistance besides PSA which in my opinion is to late.
The failure mechanisms I have found so far are
1) Aldoketo Reductase 1C3 which is back door for DHT production.
2) Neuroendocrine which is a very bad cancer to get and is small cell cancer that is similar to small cell lung cancer and treated the same as SCLC.
3) There are no AR variants or androgen dependency that I have found thus I don't see a treatment that utilizes androgens as a further treatment such as anothe AR inhibitor nor Superphysiological Testosterone like in BAT protocol.
I recently found an early marker for neuroendocrine PCa and it is LDH (Lactate Dehydrogenase).
Advances in neuroendocrine prostate cancer research: From model construction to molecular network analyses
nature.com/articles/s41374-...
"In addition, before the diagnosis of t-NEPC, changes may be observed in the pathological and molecular characteristics of the patients. For example, in certain cases, the disease progresses rapidly when PSA levels are low, liver metastasis is detected shortly after the detection of elevated lactate dehydrogenase (LDH) levels, and “non-AR-driven” characteristics appear immediately after the loss of TP53 or RB140. These results indicate that the expression of these “predictive” factors should be tested earlier for the early diagnosis of NEPC."
Second generation androgen receptor antagonists and challenges in prostate cancer treatment
ncbi.nlm.nih.gov/pmc/articl...
" The utility of these agents has expanded with the emergence of second-generation AR antagonists, which began with the approval of enzalutamide in 2012 by the United States Food and Drug Administration (FDA). Together with apalutamide and darolutamide, which were approved in 2018 and 2019, respectively, these agents have improved the survival of patients with prostate cancer, with applications for both androgen-dependent and castration-resistant disease. While patients receiving these drugs receive a benefit in the form of prolonged survival, they are not cured and ultimately progress to lethal neuroendocrine prostate cancer (NEPC). Here we summarize the current state of AR antagonist development and highlight the emerging challenges of their clinical application and the potential resistance mechanisms, which might be addressed by combination therapies or the development of novel AR-targeted therapies."