Novel agents in renal carcinoma: a reality check

Abstract

Abstract:The discovery of the molecular mechanisms underlying development of renal cell carcinoma have allowed for the development of novel targeted therapy for treatment of this disease. Recently, multiple agents have become approved by regulatory authorities for the treatment of advanced renal cell carcinoma, including sunitinib, sorafenib, bevacizumab (with interferon alpha), pazopanib, temsirolimus and everolimus. While these therapies have generated excitement and have clearly altered the treatment paradigm, multiple limitations have been elucidated over time. These include but are not limited to the fact that treatment is not associated with complete responses, a significant number of patients are primarily refractory to treatment, and clinical trials mostly include clear cell histology. Furthermore, the role of these therapies in the treatment of brain metastases remains unclear and therapies can have considerable toxicities. RECIST criteria (Response Evaluation Criteria In Solid Tumors) can be inadequate for the assessment of these modalities' treatment efficacy, and biomarkers predictive of individual patient benefit have been elusive. This review summarizes the major clinical data and discusses these limitations.

Dysregulated D-dopachrome Tautomerase, a Hypoxia-inducible Factor-dependent Gene, Cooperates with Macrophage Migration Inhibitory Factor in Renal Tumorigenesis

“…(26). However, variable efficacies and tumor resistance to these treatments have emerged as major problems.…”

Temsirolimus for advanced renal cell carcinoma

“…In the absence of pivotal trials, recommendations round about temsirolimus based on subgroup analysis of the temsirolimus registration trial and case reports cannot be made. However, data show that patients may benefit from treatment with temsirolimus [31,73,[75][76][77][78][79]. Regarding this issue, Bojanapally et al have presented their results when administering temsirolimus in patients who had received prior systemic therapy [80].…”

Effects of the novel heat shock protein 90 inhibitor AUY922 in renal cell carcinoma ACHN and 786-O cells

“…Radical surgery remains the only potentially curative therapeutic option for RCC (14). Although an increased number of small renal masses are being detected, approximately one-third of patients present with metastatic disease (15). Metastatic RCC has demonstrated a poor response to chemotherapy and hormonal therapy.…”

“…cDNA was synthesized from 2 µg of total RNA using a Reverse Transcription System kit (Promega, Madison, WI, USA), according to the following protocol obtained from the reaction kit. Briefly, the samples were pre-incubated at 70˚C for 10 min, cooled on ice and then added to a reaction mixture consisting of 10 mmol/l deoxynucleotide triphosphate mixture, 25 mmol/l MgCl 2 , 15 units avian myoblastosis virus reverse transcriptase, 10X reverse transcription buffer, 0.5 units RNasin ® and 0.5 µg oligo-(dT) 15 primer (all provided with the Reverse Transcription System kit). The reaction mixture was made up to a final volume of 20 l and was incubated successively at 44˚C for 15 min, 99˚C for 5 min and 4˚C for 5 min.…”