REVIEW | doi:10.20944/preprints202208.0163.v1
Subject: Medicine & Pharmacology, Urology Keywords: STAT3; prostate cancer; bladder cancer; upper tract urothelial carcinoma; renal cell carcinoma; penile cancer; testicular cancer
Online: 8 August 2022 (15:09:21 CEST)
Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.
REVIEW | doi:10.20944/preprints202207.0393.v1
Subject: Medicine & Pharmacology, Urology Keywords: metastatic castration-resistant prostate cancer; cancer vaccines; immunotherapy; focal therapy; combination immunotherapy; tumor immune microenvironment; in vivo vaccination
Online: 26 July 2022 (08:01:20 CEST)
Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.
REVIEW | doi:10.20944/preprints202206.0286.v1
Subject: Medicine & Pharmacology, Urology Keywords: interleukin-17; renal cell carcinoma; immunotherapy; inflammation; tumor microenviroment; tumor development; Th17 lymphocytes
Online: 21 June 2022 (05:11:36 CEST)
Nowadays molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17) - an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancer because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relation with tumors is extremely complex and constitute a recent topic for numerous research. What is worth highlighting is IL-17 dual character in cancer development - it could be pro- as well as antitumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.
REVIEW | doi:10.20944/preprints202203.0139.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: CD15; Lewis X; Lex; Cancer; Therapy
Online: 10 March 2022 (04:15:33 CET)
CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These include renal cancer, prostate and bladder cancers, acute leukemias, hepatocellular carcinoma, breast cancer and melanoma. The antigen plays an espe-cially significant role in renal cell carcinoma. Its high expression serves as a good prognostic marker for patients and high hopes are related to its use in the immunotherapy of the tumor. The biological role of CD15 is the interaction with E-, L- and P-selectins (adhesion molecules) and al-lowing for the adhesion with the endothelial cells. In this way, cancer cells start to interact with the endothelium of blood vessels and consequently move out from the blood flow to the sur-rounding tissues. The blockage of antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibod-ies-based therapies. CD15s is a sialyl derivative of CD15, that possess its own unique characteris-tics. Unlike high expression of CD15, which is a prognostic factor in Hodgkin lymphoma, CD15s relate to poor prognosis for the patients. Due to the high abundance in cancer cells, CD15 is con-sidered as a marker of Cancer Stem Cells. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews the clinical appli-cations of the anti-CD15 therapy.