Evolving therapeutic targets in renal cell carcinoma

  title={Evolving therapeutic targets in renal cell carcinoma},
  author={Eric A. Singer and Gopal N. Gupta and Daniel Marchalik and Ramaprasad Srinivasan},
  journal={Current Opinion in Oncology},
Purpose of review Recent developments in the treatment of advanced renal cell carcinoma (RCC) will be discussed, with emphasis on data published over the past year. The genetics and molecular biology of the various histologic subtypes of kidney cancer will be reviewed, as these subtle yet important genomic and metabolic alterations provide the opportunity for rational drug development and personalized treatment regimens. Recent findings Additional targeted agents continue to be added to the uro… 
Renal cell carcinoma: molecular biology and targeted therapy
The therapeutic armamentarium available to genitourinary oncologists continues to grow, but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC.
Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology
The complex molecular changes underlying individual RCC variants are yet to be fully elucidated and remain the subject of ongoing investigation, leading to the need to tailor therapeutic approaches to the unique genetic alterations specific to individual subtypes of RCC.
Identification of metabolic genes essential for proliferation of clear cell Renal Cell Carcinoma (ccRCC) cells
In conclusion, the study reported in this thesis provides insight into the metabolic dependencies of ccRCC cells and emphasises the need for a solid anti-oxidant system forccRCC cell survival and proliferation.
Hereditary renal cell carcinoma: genetics, clinical features, and surgical considerations
Identification of genetic basis of hereditary carcinomas provides opportunity for targeted therapy of metastatic sporadic renal cell carcinoma and allows for preservation of renal function despite the need for repeat surgical interventions.
Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma
It is shown that varied level of XPF expression was organ‐tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively and silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor.
Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma.
The results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.
Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins
The relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their receptors (EPO-R, V EGFR-2), and SCD-1 in early stages of ccRCC is demonstrated.
Increased Nek1 expression in Renal Cell Carcinoma cells is associated with decreased sensitivity to DNA-damaging treatment
It is suggested that Nek1 can serve as a potential therapeutic target for drug development in the treatment of RCC by maintaining persistent VDAC1 phosphorylation, closing its channel and preventing the onset of apoptosis under genotoxic insults.


Targeted therapeutic strategies for the management of renal cell carcinoma
Current and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.
Update on targeted therapies for clear cell renal cell carcinoma
O Ongoing research to identify novel agents continues to build upon the work done during the elucidation of the von Hippel-Lindau/clear cell RCC pathway, which continues to play a critical role in the management of advanced and metastatic RCC.
Targeting the mTOR pathway in Chromophobe Kidney Cancer
The experience with targeted therapy in a patient with advanced chromophobe RCC who had a durable partial response to temsirolimus is reported and the preclinical rationale for the use of mTOR inhibitors in this population based on the characterization of the hereditary form of Chromophobe kidney cancer, Birt-Hogg-Dube syndrome, is discussed.
Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
  • C. Sternberg, I. Davis, R. Hawkins
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
Temsirolimus in metastatic chromophobe renal cell carcinoma after interferon and sorafenib therapy.
The case of a patient with chRCC who experienced rapid improvement in his general condition and stable disease on treatment with temsirolimus, following disease progression on interferon alfa and sorafenib treatment is described.
Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a phase III randomized, open-label, multicenter trial.
Tivozanib, a potent, selective, long half-life tyrosine kinase inhibitor targeting all three VEGF receptors, showed activity and tolerability in a Phase II trial in patients with clear cell advanced renal cell carcinoma and prior nephrectomy.
Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma.
Frentinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patientsWith germline MET mutations, the presence of a germlineMET mutation was highly predictive of a response.
Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.
As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis.
Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma.
Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC, and additional prospective trials with these agents in non-clear cell RCC will further clarify their use in the future.