The most common subtype of renal cell carcinoma is clear cell renal cell carcinoma (ccRCC). While localized ccRCC can be cured with surgery, metastatic disease has a poor prognosis. Recently, immunotherapy has emerged as a promising approach for advanced ccRCC. This review provides a comprehensive overview of the evolving immunotherapeutic landscape for metastatic ccRCC. Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 and CTLA-4 inhibitors have demonstrated clinical efficacy as monotherapies and in combination regimens. Combination immunotherapies pairing ICIs with antiangiogenic agents, other immunomodulators, or novel therapeutic platforms such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy are areas of active research. Beyond the checkpoint blockade, additional modalities including therapeutic vaccines, cytokines, and oncolytic viruses are also being explored for ccRCC. This review discusses the mechanisms, major clinical trials, challenges, and future directions for these emerging immunotherapies. While current strategies have shown promise in improving patient outcomes, continued research is critical for expanding and optimizing immunotherapy approaches for advanced ccRCC. Realizing the full potential of immunotherapy will require elucidating mechanisms of response and resistance, developing predictive biomarkers, and rationally designing combination therapeutic regimens tailored to individual patients. Advances in immunotherapy carry immense promise for transforming the management of metastatic ccRCC.

Immunotherapy has emerged as an important approach for cancer treatment, but its clinical efficacy has been limited in prostate cancer compared to other malignancies. This review summarizes key immunotherapy strategies under evaluation for prostate cancer, including immune checkpoint inhibitors, bispecific T cell-engaging antibodies, chimeric antigen receptor (CAR) T cells, therapeutic vaccines, and cytokines. For each modality, the rationale stemming from preclinical studies is discussed along with outcomes from completed clinical trials and strategies to improve clinical efficacy that are being tested in ongoing clinical trials. Imperative endeavors include biomarker discovery for patient selection, deciphering resistance mechanisms, refining cellular therapies such as CAR T cells, and early-stage intervention were reviewed. These ongoing efforts instill optimism that immunotherapy may eventually deliver significant clinical benefits and expand treatment options for patients with advanced prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is driven by a complex network of resistance mechanisms against standard-of-care therapies, resulting in poor long-term outcomes. This review offers a uniquely comprehensive and integrative perspective on these resistance pathways, systematically examining both androgen receptor (AR)-dependent factors (including AR overexpression, point mutations, glucocorticoid receptor signaling, splice variants, post-translational modifications, altered coregulators, and intratumoral hormone biosynthesis) and AR-independent pathways (such as neuroendocrine differentiation, lineage plasticity, and alternative growth factor signaling). We also highlight resistance mechanisms influencing immunotherapy, chemotherapy, radiopharmaceutical therapy and targeted therapy. By synthesizing emerging insights across these domains, this review not only clarifies the underlying biology of mCRPC resistance but also identifies key leverage points for more effective interventions. Building on this foundation, we propose a forward-looking framework for overcoming mCRPC drug resistance, emphasizing the importance of biomarker-guided patient selection, combination strategies that simultaneously target multiple resistance mechanisms, and novel therapies under investigation. These recommendations are intended to guide future clinical trial designs and research priorities that move beyond incremental improvements. Ultimately, this comprehensive synthesis aims to serve as a resource for clinicians and researchers to accelerate the development of durable, precision-based treatment strategies in mCRPC.

Canopy FGF signaling regulator 2 (CNPY2) has emerged as a crucial player in cancer development by promoting cell proliferation, tissue repair, and angiogenesis. This review synthesizes the current understanding of CNPY2’s role in solid tumors, particularly renal cell carcinoma, prostate cancer, hepatocellular carcinoma, and non-small-cell lung cancer. CNPY2 modulates key pathways such as p53, MYLIP, NF-κB, and AKT/GSK3β, thereby driving tumor growth and progression. In renal cell carcinoma, CNPY2 paradoxically promotes tumor growth through p53 upregulation, while in hepatocellular carcinoma, CNPY2 drives cell cycle progression via p53 destabilization. In prostate cancer, it enhances tumor progression by stabilizing androgen receptors through MYLIP interaction, and in non-small-cell lung cancer, it contributes to chemoresistance and metastasis through NF-κB and AKT/GSK3β signaling. Additionally, CNPY2 influences the tumor microenvironment, impacting immune function and metastatic potential. As a potential biomarker, CNPY2 shows promise for cancer detection and prognosis, particularly when used in combination with other markers. Early therapeutic strategies, including siRNA and miRNA approaches, are under exploration, though challenges remain due to CNPY2’s expression in normal tissues and potential off-target effects. This review underscores the need for further research to fully elucidate CNPY2’s oncogenic mechanisms and develop targeted therapies. Improved understanding of CNPY2’s diverse roles may lead to novel diagnostic and therapeutic approaches in solid tumors.

Introduction: The treatment efficacy of prostate cancer (PCa) radiotherapy (RT) can be inadvertently affected by the concurrent usage of non-oncologic medications. Many studies have associated the intake of several non-oncologic drugs with cancer specific outcomes. In this study, we report the impact of daily non-oncologic medications including aspirin, metformin, and statins on time to progression for patients with high-risk PCa. Methods: Patients with high- and very high risk PCa (NCCN definition of Gleason score ≥ 8, prostate-specific antigen (PSA) ≥ 20, or ≥cT3a) who received definitive RT at two institutions were included in this analysis. Progression was defined as either biochemical (PSA > nadir + 2 ng/mL), locoregional (prostate or lymph nodes, biopsy-proven), or development of distant metastases. Progression-free survival (PFS) was defined as the time elapsed from the start of RT to progression or last follow-up. Cox proportional hazards models evaluated the associations between non-oncologic medications and PFS. Results: There were 237 patients eligible for this analysis, of which 47 (19.8%) and 178 (75.1%) had at least clinical T3 disease or at least Gleason 8 disease, respectively. During RT, 82 (34.6%), 88 (37.1%), and 29 (12.2%) patients were taking aspirin, statin, or metformin, respectively. Overall, 54 patients (22.8%) experienced disease progression. Neither aspirin nor statin usage had a significant association with PFS. Patients prescribed metformin displayed worse PFS compared to patients not taking metformin (aHR: 2.46, 95% CI: 1.06–5.72). Conclusions: Aspirin and statin usage was not associated with likelihood of progression in this large cohort of patients with high-/very high risk PCa. Metformin use was associated with poorer PFS, albeit with a small event rate due to fewer patients taking metformin. Further studies are needed to clarify the impact of common non-oncologic medication use on outcomes for patients with high-risk PCa.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized metastatic NSCLC treatment. Acute kidney injury (AKI) is a common complication of ICI‐based therapies, alone or with chemotherapy. This study investigates the association between early AKI and 12‐month survival among patients with metastatic NSCLC receiving front‐line ICI‐based treatment. Methods: This retrospective study included metastatic NSCLC patients who received ICI‐based therapy (2017–2022). Early AKI was defined as a creatinine increase ≥ 1.5 times baseline within 21 days of the fourth cycle or last cycle if fewer than four were given. Clinical characteristics were compared using t‐tests and chi‐squared tests. Survival differences were assessed by Kaplan–Meier and log‐rank tests, with Cox models evaluating the association between AKI and 12‐month survival. Results: Of the 310 patients, AKI occurred in 38 patients (12.6%), with 8 patients (2.3%) missing follow‐up creatinine data. The hazard ratio (HR) for death within 12 months for patients who developed early AKI was 1.733 (95% CI 1.060–2.835, p = 0.026). The highest rate of early AKI was seen in patients receiving pemetrexed, pembrolizumab, and carboplatin (16.7%), compared to 11.1% for pembrolizumab monotherapy and 4.5% for pembrolizumab with paclitaxel and carboplatin. Although patients who recovered renal function were more likely to continue immunotherapy, 12‐month survival rates did not significantly differ (52.2% vs. 46.7%). Conclusions: Early AKI during pembrolizumab‐based treatment in metastatic NSCLC patients was associated with reduced 12‐month survival. These findings highlight the need for close monitoring and preventive strategies to manage AKI in this population.