Review on Targeted Treatment of Patients with Advanced-Stage Renal Cell Carcinoma: A Medical Oncologist's Perspective

Asian Pac J Cancer Prev, 15 (7), [3045][3046][3047][3048][3049][3050] IntroductionRenal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common in women. It also accounts for 2% to 3% of all malignant diseases in adults (Rini et al., 2009). The incidence of this cancer has increased, probably contributing to the aging of population (Rini et al., 2009; Cairn, 2010). Radical or partial nephrectomy is the major surgical treatment for local RCC according to the size of carcinoma. For patients having recurrent metastatic RCC, systemic treatment is preferred. However, the overall survival of patients with RCC remains unsatisfactory because of the high incidence of recurrence and metastasis after treatment, especially for those having metastatic RCC (Cohen et al., 2005;Rini et al., 2009;Grunwald et al., 2014). Thus, inhibition of the progress, recurrence, and metastasis of the tumor is of great importance in the treatment of RCC.Angiogenesis is indispensable in the promotion of invasive tumor growth and metastasis; it is also an important factor that controls cancer progression. For

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confidence: 99%

Targeting EGFL7 Expression through RNA Interference Suppresses Renal Cell Carcinoma Growth by Inhibiting Angiogenesis

Chen²,

Liu³

et al. 2014

“…However, radical nephrectomy assisted with INF-α and IL-2 cytokine therapy could not efficiently decrease recurrency and metastasis (Tanriverdi, 2013). Therefore, investigation of active immunotherapy of a possible DC tumor vaccine plays a crucial role for a future clinical application (Ramsey et al, 2006;Passalacqua et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Heat-Shock Protein 70 as a Tumor Antigen for in vitro Dendritic Cell Pulsing in Renal Cell Carcinoma Cases

Meng

Sui²,

Tian³

et al. 2014

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-α. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-α. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

“…Better definition of signal message pathways playing a role in the development of RCC has caused an increase in preclinical and clinical studies into directed treatment of RCC (Tanriverdi, 2013). An evolving appreciation of the therapeutic limits of the current agents (including antiangiogenic, molecularly targeted, and immunotherapeutic) has heightened the need for continued exploration of RCC biology and investigation of novel approaches to RCC management (Philips and Atkins, 2014).…”

Section: Discussionmentioning

confidence: 99%

ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

Liu

Wu²,

Liu³

et al. 2015

Hyperactivated α2-6-sialylation on N-glycans due to overexpression of the Golgi enzyme β-galactoside: α2-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.