Renal cell carcinoma: Resistance to therapy, role of apoptosis, and the prognostic and therapeutic target potential of TRAF proteins

Renal cell carcinoma (RCC) is the commonest of the renal neoplasms. Although surgery and cryoablation are successful curative treatments for localized RCC, most patients are diagnosed with advanced or metastatic RCC, which has a poor prognosis. RCC are a heterogeneous set of cancers that have traditionally been classified and staged using cellular characteristics, size, local extension and distant metastases. Current staging systems provide good prognostic information, but it is very likely that the identification of new more accurate and predictive prognostic markers, not currently included in traditional staging systems, will improve the outcome for RCC patients. For this reason, increased knowledge of the underlying molecular characteristics of RCC development and progression is necessary. In most cancers, but especially RCC, deregulated control of apoptosis contributes to cancer growth by aberrantly extending cell viability and facilitating resistance to cancer therapies. Here we present the hypothesis that select members of the tumor necrosis factor (TNF) superfamily, the TNF receptor-associated factors (TRAFs), have a role in RCC apoptosis and may have prognostic significance for RCC. Candidate biomarkers for RCC are few, and the TRAFs may be important inclusions in panels of biomarkers for RCC. TRAFs may also be potential molecular targets for new therapies, either through their ability to promote apoptosis in the cancers themselves, or through their ability to modulate the immune defence against cancer progression. Some support data are presented here for our hypothesis. However, these novel concepts need further careful analysis to allow clinicians and oncologists any assistance for earlier detection of RCC and for characterizing patients with RCC for individualised targeted therapy.