Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant renal tumors constitute 3% of human cancers, although their frequency differs greatly in various areas. Since the fifties, the incidence of renal cancers has been increasing, but at the some time the prognosis has been improving. In particular, in the last years, several new treatment modalities have been introduced, relying on the understanding of renal cancer biology. The identified etiological factors include smoking, increased body mass, dietary factors and chronic renal disease. There are several renal tumor types differing in morphology, molecular genetics and biology. Inactivation of the VHL gene leads to formation of the most frequent form in adults, namely clear cell carcinoma. The VHL gene product, a component of an ubiquitin-ligase complex, regulates expression of several genes. Papillary carcinomas depend mainly on the HGF receptor gene (c-Met) activating mutations. At least two types of papillary carcinomas exist, which have different morphology and prognosis. The molecular biology of chromophobe carcinoma and oncocytoma is poorly understood. Differential diagnosis of these tumors is particularly difficult and may require extensive immunohistochemical and molecular studies. Collecting duct carcinoma and medullary carcinoma are extremely aggressive but rare tumors. Some renal tumors have been described or recognized only relatively recently; these newer entities include multilocular cystic clear cell carcinoma, spindle cell papillary mucinous carcinoma, tubulocystic carcinoma, renal epithelial and stromal tumor, epithelioid and oncocytic angiomyolipoma. Besides histological typing, the prognostic factors include tumor stage, grade and several immunohistochemical and molecular markers that are currently under elaboration. The improved prognosis in renal cancer depends on earlier detection, but also on refinement of therapeutic methods. Small tumors may currently be treated by partial nephrectomy or radiofrequency ablation and larger ones by a laparoscopic approach. All these methods seem to give satisfactory results with low morbidity and mortality rates. Renal carcinoma is notorious for its low sensitivity to chemotherapy and radiotherapy. For several years, immunological treatment with IL-2 and INF-alpha was the only adjuvant therapy method. However, recently several new drugs have been introduced; they act on tyrosine-kinase receptors, VEGF, c-Met or mTOR pathway. With this progress, perfect understanding of renal tumor biology and exact histological diagnosis have become of prime practical importance.
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PMID:Pathology of renal tumors in adults. Molecular biology, histopathological diagnosis and prognosis. 1909 56

Non-clear cell renal cell carcinomas (nccRCC) are rare diseases with heterogeneous histopathologically and genetically defined entities. The clinical data on optimal systemic treatments of nccRCC is rather limited. In this review, the current World Health Organization (WHO) classification of nccRCC based on histopathologic and genetic findings is reported. Regarding systemic treatment options, the most commonly used agents are mTOR inhibitors like everolimus or temsirolimus, or tyrosine kinase inhibitors like sunitinib. 2 small randomized clinical trials with nccRCC comparing sunitinib with everolimus revealed a trend towards a better progression-free survival (PFS) and overall survival (OS) in favor of sunitinib. In RCC with predominant sarcomatoid features, both chemotherapy and targeted agents are reported without any preference for outcome. For subsequent lines of therapy, some case reports describe promising effects of PD-1 or PD-L1 inhibitors in nccRCC including sarcomatoid subtype and Bellini duct carcinoma. Currently, nccRCCs are treated similarly to clear cell RCC or, whenever possible, within clinical trials. Clinical trials with immune checkpoint inhibitors are ongoing.
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PMID:Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options. 3079 4