Abstract
Signal Transducer and Activator of Transcription (STAT) proteins have been identified as drivers of prostate cancer (PCa) progression and development of aggressive castration-resistant phenotypes. In particular, STAT3, 5, and 6 have been linked to resistance to androgen receptor inhibition and metastasis in in vitro and in vivo models. This descriptive study aimed to validate these preclinical data in tissue obtained from patients with PCa before and while under androgen-deprivation therapy. Therefore, STAT3, 5, and 6 expressions and activity were assessed by immunohistochemistry. The data revealed that STAT3 and 5 changed in PCa. However, there was no relationship between expression and survival. Moreover, due to the heterogeneous nature of PCa, the preclinical results could not be transferred congruently to the patient’s material. A pilot study with a longitudinal patient cohort could also show this heterogeneous influence of systemic therapy on STAT3, 5, and 6 expressions and activity. Even if the main mechanisms were validated, these data demonstrate the urge for better patient-near preclinical models. Therefore, these data reflect the need for investigations of STAT proteins in a longitudinal patient cohort to identify factors responsible for the diverse influence of system therapy on STAT expression.
Highlights
Prostate cancer (PCa) is one of the most common cancers in men, with an estimated number of over 1.4 million new cases worldwide in 2020
Since PCa is androgen dependent in its growth, first-line therapy includes androgen-deprivation therapy (ADT), which is indicated for metastasized hormone-sensitive PCa and can be combined with taxan-based chemotherapy (CTx) or novel hormonal therapy (NHT) as apalutamide, abiraterone, or enzalutamide [2,4]
For ADT + NHT, ADT combined with enzalutamide or abiraterone was administered
Summary
Prostate cancer (PCa) is one of the most common cancers in men, with an estimated number of over 1.4 million new cases worldwide in 2020. Organ-confined PCa (TMN stage 1 and 2) is treated with curative intent by radical prostatectomy or radiation therapy [2]. For these patients, 5-year survival is 100% [3]. In patients with metastasized PCa (TMN stage 3 and 4) 5-year survival is ~30% [3]. Treatment for metastasized CRPC (mCRPC) includes taxane-based chemotherapy with docetaxel or cabazitaxel, abiraterone, and the antiandrogen enzalutamide [4]. Despite recent improvements in treatment options, patients suffering from mCRPC only have a median life expectancy of 19 months due to tumor progress and emerging therapy resistance [5]
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