The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies.

With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.

Emerging strategy for the treatment of urothelial carcinoma: Advances in antibody-drug conjugates combination therapy.

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.

Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review.

Bipolar androgen therapy (BAT) is a new endocrinologic treatment for castration-resistant prostate cancer (CRPC) that can restore some patients' sensitivity to drugs such as abiraterone (Abi) and enzalutamide (Enz). We performed a meta-analysis using STATA16. Sensitivity analyses were performed by examining the effects of individual studies using different effect models and detecting any publication bias using the Harbord test. In a total of 108 unique records, ten studies were included in the final meta-analysis. Participants who underwent BAT achieved a PSA50 response rate of 27% (95%CI [0.22,0.31], I2=17.98%), ORR of 34% (95%CI [0.24,0.43], I2=0), and incidence of AEs (grade≥3) of 14% (95%CI [0.09,0.19], I2=0). Patients who completed BAT proceeded to AR-targeted therapy (Abi or Enz) and achieved a PSA50 response rate of 57% (95% CI [0.36,0.78], I2=0). Patients with prior Enz resistance had a stronger impact on the PSA50 of AR-target therapy rechallenge. The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz. BAT can trigger the resensitization of patients with CRPC to subsequent endocrine therapy and improve the overall survival of patients and their quality of life.

Renal cell carcinoma of different pathological types in bilateral native kidneys of a kidney transplant recipient: A case report and literature review.

Patients after kidney transplantation have a much higher risk of developing malignant tumors than the general population. And the native kidney is an organ relatively susceptible to malignant tumors after renal transplantation. However, the simultaneous development of bilateral renal tumors is very rare; especially the bilateral native kidneys harbor different pathological types of renal cell carcinoma (RCC). We report a case of a patient who developed malignant tumors in both native kidneys nearly 19 years after renal transplantation. This patient underwent bilateral laparoscopic radical nephrectomy, and postoperative pathological examination showed clear cell RCC on the left native kidney and papillary RCC on the right one. And the early detection and surgical treatment resulted in a good prognosis. The literature related to the diagnosis and treatment of bilateral RCC after renal transplantation is also reviewed.

Suppressing BCL-XL increased the high dose androgens therapeutic effect to better induce the Enzalutamide-resistant prostate cancer autophagic cell death.

Most patients with advanced prostate cancer (PCa) initially respond well to androgen deprivation therapy (ADT) with antiandrogens, but most of them eventually become resistant to ADT. Here, we found that the antiandrogen Enzalutamide-resistant (EnzR) PCa cells can be suppressed by hyper-physiological doses of the androgen DHT. Mechanism dissection indicates that while androgens/androgen receptor (AR) can decrease BCL-2 expression to induce cell death, yet they can also simultaneously increase anti-apoptosis BCL-XL protein expression via decreasing its potential E3 ubiquitin ligase, PARK2, through transcriptionally increasing the miR-493-3p expression to target PARK2. Thus, targeting the high dose DHT/AR/miR-493-3p/PARK2/BCL-XL signaling with BCL-XL-shRNA can increase high-dose-DHT effect to better suppress EnzR cell growth via increasing the autophagic cell death. A preclinical study using in vivo mouse model also validated that suppressing BCL-XL led to enhance high dose DHT effect to induce PCa cell death. The success of human clinical trials in the future may help us to develop a novel therapy using high dose androgens to better suppress CRPC progression.