Abstract A03: Comprehensive predictive biomarker evaluation in two phase II clinical trials of the PI3K/mTOR inhibitor GDC-0980 in metastatic renal cell carcinoma and advanced endometrial cancer

Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by osteoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.

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Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials

European Journal of Cancer ◽

10.1016/j.ejca.2021.06.015 ◽

2021 ◽

Vol 154 ◽

pp. 120-127

Author(s):

Francesco Massari ◽

Alessandro Rizzo ◽

Veronica Mollica ◽

Matteo Rosellini ◽

Andrea Marchetti ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis ◽

Randomised Clinical Trials

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Long Noncoding RNA HOTTIP Serves as an Independent Predictive Biomarker for the Prognosis of Patients with Clear Cell Renal Cell Carcinoma

International Journal of Genomics ◽

10.1155/2020/4301634 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Zhanxin Liu ◽

Zichun Wang ◽

Xiaoxiong Wang ◽

Meisong Lu ◽

Guang Chen

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Noncoding Rna ◽

Clear Cell ◽

Clinical Stage ◽

Predictive Biomarker ◽

The Cancer Genome Atlas ◽

Cell Renal Cell Carcinoma ◽

Advanced Clinical Stage

Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, p<0.0001). The result also showed that elevated HOTTIP expression was correlated with more LNM (OR=2.61, 95% CI 1.91-3.58, p<0.0001) and advanced clinical stage (OR=3.57, 95% CI 2.58-4.93, p<0.0001). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.

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Systemic adjuvant therapies in renal cell carcinoma

Oncology Reviews ◽

10.4081/oncol.2012.e18 ◽

2012 ◽

Vol 6 (2) ◽

pp. 18 ◽

Cited By ~ 6

Author(s):

Sebastiano Buti ◽

Melissa Bersanelli ◽

Maddalena Donini ◽

Andrea Ardizzoni

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Cell Carcinoma ◽

Renal Cell ◽

Radical Surgery ◽

New Drugs ◽

Phase Iii ◽

Current Standard ◽

Adjuvant Therapies ◽

Systemic Treatments

Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

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