Therapeutic Options for Variant Renal Cancer

Stadler, Walter M.

doi:10.1158/1078-0432.ccr-040032

Cited by 13 publications

(5 citation statements)

References 31 publications

(26 reference statements)

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“…Unlike the role of VHL in clear cell RCC, Met mutations are rare in sporadic papillary renal cancers. Even though RCC is subdivided for clinical description as papillary type I, type II, clear cell, etc., pathologic features with mixed histologies are commonly observed (94). This underscores the possible overlapping mechanisms that could be common denominators for all these subtypes.…”

Section: Role Of Carbonic Anhydrases In Papillary Type I Rccmentioning

confidence: 78%

Role of Carbonic Anhydrases in the Progression of Renal Cell Carcinoma Subtypes: Proposal of a Unified Hypothesis

Dorai¹,

Sawczuk²,

Pastorek³

et al. 2006

Cancer Investigation

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Renal cell carcinoma (RCC) has the highest rate of occurrence within the US when compared with other countries. Recent advances in the basic research and molecular diagnostics of this malignancy have revealed that RCC is not a single disease, but it is a mixture of several types of malignancies with unique molecular mechanisms and pathological attributes. RCC is now divided into clear cell carcinoma (80% of all kidney cancers), papillary type 1 and papillary type 2 neoplasms (10-15% of all RCC patients) and RCC with chromophobic and oncocytic features, called the Birt-Hogg-Dube (BHD) subtype, in roughly 5% of all patients. Apart from these, neoplasms such as the tuberous sclerosis (TSC) syndrome may occur with a mixed pathological features with a renal presentation. In this review, molecular evidence, both direct and indirect, published so far on all these RCC subtypes have been analyzed to find out whether there is any common thread that could run through these disparate malignancies that happen to occur in a single organ, i.e., the kidney. We believe that the role played by the expression and certain non-traditional activities of the cabonic anhydrase (CA) family members, along with the differing levels of hypoxia induced within these tumors may be the most common denominators. Evidence is presented focusing on how the CA family members could participate in the genesis and progression of each and every one of these RCC subtypes and how their function could be influenced by hypoxia, activities of receptor type protein tyrosine kinases and certain other pre-disposing factors. These rationalizations point towards a unified hypothesis that may help explain the occurrence of all these RCC subtypes in a molecular manner. We hope that these analyses would a) stimulate further studies aimed toward a better understanding of the role played by carbonic anhydrases in RCC subtypes and b) would pave way to a better and rationally designed therapies to interfere with their function to benefit patients with RCC and possibly other cancers.

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Section: Role Of Carbonic Anhydrases In Papillary Type I Rccmentioning

confidence: 78%

Role of Carbonic Anhydrases in the Progression of Renal Cell Carcinoma Subtypes: Proposal of a Unified Hypothesis

Dorai¹,

Sawczuk²,

Pastorek³

et al. 2006

Cancer Investigation

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“…The study of new drugs is warranted since effective systemic therapy has not been identified for papillary RCC. Histological subgroup analyses of clinical trials and a clinical registry have been suggested as ways to better evaluate experimental agents in this population [14].…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma

et al. 2006

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The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.

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“…Recently, classical molecular genetics, cytogenetics, and expression profiling have clarified some of the relationships among the various histologic subtypes of RCC [6][7][8][9]. Despite the power of molecular profiling from the diagnostic and therapeutic viewpoints, it is most important to identify molecular alterations critical in the initiation and progression of the malignant phenotype of a specific tumor [10]. The results of cDNA profilings support the existence of an individual fingerprint for each RCC subtype regarding its biological features, clinical behavior, and unique sensitivity to therapy.…”

Section: Introductionmentioning

confidence: 99%

Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma

Seliger¹,

Lichtenfels²,

Atkins³

et al. 2005

Proteomics

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Renal cell carcinoma (RCC) representing the most common neoplasia of the kidney in Western countries is a histologic diverse disease with an often unpredictable course. The prognosis of RCC is worsened with the onset of metastasis, and the therapies currently available are of limited success for the treatment of metastatic RCC. Although gene expression analyses and other methods are promising tools clarifying and standardizing the pathological classification of RCC, novel innovative molecular markers for the diagnosis, prognosis, and for the monitoring of this disease during therapy as well as potential therapeutic targets are urgently needed. Using proteome-based strategies, a number of RCC-associated markers either over-expressed or down-regulated in tumor lesions in comparison to the normal epithelium have been identified which have been implicated in tumorigenesis, but never linked to the initiation and/or progression of RCC. These include members of the fatty acid binding protein family, which have the potential to serve as diagnostic or prognostic markers for the screening of RCC patients.

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Therapeutic Options for Variant Renal Cancer

Cited by 13 publications

References 31 publications

Role of Carbonic Anhydrases in the Progression of Renal Cell Carcinoma Subtypes: Proposal of a Unified Hypothesis

Role of Carbonic Anhydrases in the Progression of Renal Cell Carcinoma Subtypes: Proposal of a Unified Hypothesis

A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma

Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma

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