Contribution of LAT1-4F2hc in Urological Cancers via Toll-like Receptor and Other Vital Pathways

Tumor cells are known for their ability to proliferate. Nutrients are essential for rapidly growing tumor cells. In particular, essential amino acids are essential for tumor cell growth. Tumor cell growth nutrition requires the regulation of membrane transport proteins. Nutritional processes require amino acid uptake across the cell membrane. Leucine, one of the essential amino acids, has recently been found to be closely associated with cancer, which activate mTOR signaling pathway. The transport of leucine into cells requires an L-type amino acid transporter protein 1, LAT1 (SLC7A5), which requires the 4F2 cell surface antigen heavy chain (4F2hc, SLC3A2) to form a heterodimeric amino acid transporter protein complex. Recent evidence identified 4F2hc as a specific downstream target of the androgen receptor splice variant 7 (AR-V7). We stressed the importance of the LAT1-4F2hc complex as a diagnostic and therapeutic target in urological cancers in this review, which covered the recent achievements in research on the involvement of the LAT1-4F2hc complex in urinary system tumors. In addition, JPH203, which is a selective LAT1 inhibitor, has shown excellent inhibitory effects on the proliferation in a variety of tumor cells. The current phase I clinical trials of JPH203 in patients with biliary tract cancer have also achieved good results, which is the future research direction for LAT1 targeted therapy drugs.

Association between Human Papillomavirus and Urological Cancers: An Update

Human papillomavirus (HPV) is currently the most common sexually transmitted pathogen in the world, and as such imposes a substantial global burden due to its oncogenic properties. The significant association of HPV with anogenital and head and neck carcinomas is well established. In terms of urological malignancies, only the association between HPV and penile cancer has been well defined; despite close anatomical proximity, its relationship with bladder, prostate, kidney, and testicular cancers has remained unclear. With technological advances in the nucleic acid amplification tests used to detect HPV over the last two decades, the results of new studies have led to the need to reexamine these relationships. This brief review aims to evaluate the association between urological malignancies and HPV infection in light of recent data.

Fucosylation in Urological Cancers

Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.

Urologic Cancer Molecular Biology

An adequate understanding of the molecular mechanisms of the most common urological cancers is necessary for a correct approach to diagnosis, precise treatment, but also for the follow-up of these patients. It is necessary to understand the molecular mechanisms underlying the carcinogenic processes, the molecular pathways involved in this process, and also to describe the biomarkers useful for diagnosis but also for predictability, treatment, and natural history. In addition, it would be useful to describe a list of useful molecules currently under investigation as possible biomarkers to improve the income of cancer patients.

Diverse Roles and Therapeutic Potentials of Circular RNAs in Urological Cancers

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, which are mainly formed as a loop structure at the exons caused by noncanonical splicing; they are much more stable than linear transcripts; recent reports have suggested that the dysregulation of circRNAs is associated with the occurrence and development of diseases, especially various human malignancies. Emerging evidence demonstrated that a large number of circRNAs play a vital role in a series of biological processes such as tumor cell proliferation, migration, drug resistance, and immune escape. Additionally, circRNAs were also reported to be potential prognostic and diagnostic biomarkers in cancers. In this work, we systematically summarize the biogenesis and characteristics of circRNAs, paying special attention to potential mechanisms and clinical applications of circRNAs in urological cancers, which may help develop potential therapy targets for urological cancers in the future.