Implementation of antibody-drug conjugates in HER2-positive solid cancers: Recent advances and future directions.

In recent decades, there has been a surge in the approval of monoclonal antibodies for treating a wide range of hematological and solid malignancies. These antibodies exhibit exceptional precision in targeting the surface antigens of tumors, heralding a groundbreaking approach to cancer therapy. Nevertheless, monoclonal antibodies alone do not show sufficient lethality against cancerous cells compared to chemotherapy. Consequently, a new class of anti-tumor medications, known as antibody-drug conjugates (ADCs), has been developed to bridge the divide between monoclonal antibodies and cytotoxic drugs, enhancing their therapeutic potential. ADCs are chemically synthesized by binding tumor-targeting monoclonal antibodies with cytotoxic payloads through linkers that are susceptible to cleavage by intracellular proteases. They combined the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity and boasting superior lethality over standalone targeted drugs. The human epidermal growth factor receptor (HER) family, which encompasses HER1 (also known as EGFR), HER2, HER3, and HER4, plays a key role in regulating cellular proliferation, survival, differentiation, and migration. HER2 overexpression in various tumors is one of the most frequently targeted antigens for ADC therapy in HER2-positive cancers. HER2-directed ADCs have emerged as highly promising treatment modalities for patients with HER2-positive cancers. This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

Novel agents and clinical trials in castration-resistant prostate cancer: latest updates from 2023 ASCO-GU Cancers Symposium.

Numerous novel and effective therapeutic agents and clinical trials addressing castration-resistant prostate cancer (CRPC) were reported during the 2023 American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.

Novel ADCs and combination therapy in urothelial carcinoma: latest updates from the 2023 ASCO-GU Cancers Symposium.

Antibody-drug conjugates (ADCs) combine the cytotoxicity of small-molecule drugs with antibody targeting. Due to their precise and powerful effect, they have become a new hotspot and an important trend in the research and development of anti-tumor antibody drugs. Every year, exciting new developments and innovations in the treatment of urological tumors are introduced at the American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. In this article, we summarize some of the most impressive advances in new clinical trials and clinical data on ADCs in the 2023 ASCO-GU Cancers Symposium for the treatment of urothelial carcinoma.

Liquid biopsy in urothelial carcinoma: Detection techniques and clinical applications.

The types of urothelial carcinoma (UC) include urothelial bladder cancer and upper tract urothelial carcinoma. Current diagnostic techniques cannot meet the needs of patients. Liquid biopsy is an accurate method of determining the molecular profile of UC and is a cutting-edge and popular technique that is expected to complement existing detection techniques and benefit patients with UC. Circulating tumor cells, cell-free DNA, cell-free RNA, extracellular vesicles, proteins, and metabolites can be found in the blood, urine, or other bodily fluids and are examined during liquid biopsies. This article focuses on the components of liquid biopsies and their clinical applications in UC. Liquid biopsies have tremendous potential in multiple aspects of precision oncology, from early diagnosis and treatment monitoring to predicting prognoses. They may therefore play an important role in the management of UC and precision medicine.

Associations between lumbar bone mineral density, serum 25-hydroxyvitamin D and history of kidney stones in adults aged 30-69 years in the USA (NHANES 2011-2018).

OBJECTIVES: Most kidney stones contain calcium, which is closely associated with human bone health. Therefore, we aimed to determine the relationship between the history of kidney stones and human bone health. This study examined the associations between lumbar bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD) and a history of kidney stones in individuals aged between 30 years and 69 years. DESIGN AND DATA ANALYSIS: A multivariate logistic regression model was used to estimate the relationship between lumbar BMD, serum 25-OHD levels and kidney stones in this cross-sectional study. All models incorporated survey sample weights and were adjusted for covariates. SETTING: National Health and Nutrition Examination Survey (NHANES) 2011-2018. The exposure and outcomes of this study included the lumbar BMD and presence of kidney stones. PARTICIPANTS: All the 7500 participants for this cross-sectional survey were selected from the NHANES between 2011 and 2018. MAIN OUTCOME MEASURES: The main outcome of this study was the presence of kidney stones. The interviewers asked the questions on kidney stones while the respondents were at home, using a computer-assisted personal interview system. RESULTS: Lumbar BMD was negatively correlated with a history of kidney stones in all three multivariate linear regression models; the negative association existed in all genders after adjusting for all confounding factors. In the multiple regression analysis, there was an interaction between serum 25-OHD and lumbar BMD (p<0.05) regarding the influence on kidney stones; the negative association between lumbar BMD and kidney stones was more obvious in the higher 25-OHD group (≥50 nmol/L). CONCLUSION: The study results suggest that maintaining a high lumbar BMD may reduce the incidence of kidney stone formation. Simultaneously, maintaining a high serum 25-OHD level may be more beneficial in preventing the occurrence or recurrence of stones while ensuring a high lumbar BMD.

Blood-based liquid biopsy: insights into early detection, prediction, and treatment monitoring of bladder cancer.

Bladder cancer (BC) is a clinical challenge worldwide with late clinical presentation, poor prognosis, and low survival rates. Traditional cystoscopy and tissue biopsy are routine methods for the diagnosis, prognosis, and monitoring of BC. However, due to the heterogeneity and limitations of tumors, such as aggressiveness, high cost, and limited applicability of longitudinal surveillance, the identification of tumor markers has attracted significant attention in BC. Over the past decade, liquid biopsies (e.g., blood) have proven to be highly efficient methods for the discovery of BC biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into the peripheral circulation and allows serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers are being extensively studied and have shown promising results in clinical applications of BC, including early detection, detection of microscopic residual disease, prediction of recurrence, and response to therapy. Therefore, in this review, we aim to provide an update on various novel blood-based liquid biopsy markers and review the advantages and current limitations of liquid biopsy in BC therapy. The role of blood-based circulating tumor cells, circulating tumor DNA, cell-free RNA, exosomes, metabolomics, and proteomics in diagnosis, prognosis, and treatment monitoring, and their applicability to the personalized management of BC, are highlighted.