title: Perspectives in drug development for metastatic renal cell cancer.
abstract: Patients with renal cell carcinoma (RCC) exhibit a spectrum of clinical outcomes, with some patients following an indolent clinical course and others displaying rapidly advancing disease. As evidence points to RCC being largely refractory to traditional chemotherapy and radiotherapy strategies, immunotherapeutic approaches played a dominant role in the management of metastatic RCC for a quarter of a century. Management of this challenging tumor has been revolutionized by the incorporation of molecularly targeted therapies such as inhibitors of pathways involving tyrosine kinase signaling and the mammalian target of rapamycin (mTOR). The improvements in disease stabilization and survival seen with these agents has meant that molecularly targeted therapy now forms the foundation for treating RCC and has resulted in a multitude of studies investigating similar compounds for efficacy in RCC. Despite this, the rationale for using immunomodulatory regimens remains strong and its ongoing place in this era of targeted treatments continues to pose interesting clinical questions. The challenge of maintaining durable responses from our current therapies persists and this review highlights the plethora of options now available in RCC treatment and the directions in which modern management are heading.
authors.affiliation: University Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, UK. Bristi.basu@cancer.org.uk
authors.forename: Bristi
authors.initials: B
authors.lastname: Basu
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024221:Antineoplastic Protocols; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009362:Neoplasm Metastasis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases