Targeted therapies for non-clear renal cell carcinoma

Abstract

The treatment of advanced and metastatic kidney cancer has been revolutionized by the development of targeted systemic therapies. Despite the growing number of available agents approved for use against clear cell renal cell carcinoma, patients with non-clear histologies, constituting approximately 1 in 4 cases of kidney cancer, have not received the same attention. The majority of clinical trials testing novel targeted therapies have excluded non-clear subtypes, providing limited therapeutic options for patients with these diagnoses and their oncologists. This review will focus on the use of targeted therapies against the non-clear histologic subtypes of renal cell carcinoma: papillary I and II, chromophobe, and collecting duct. The unique genetic and molecular profiles of each distinct non-clear kidney cancer subtype will be described, as these differences are integral to the development and effectiveness of the novel agents used to treat them. Trials focusing on non-clear kidney cancer, or those that treated clear cell tumors along with significant numbers of non-clear subtypes, will be discussed. The role of cytoreductive nephrectomy and the use of neoadjuvant and adjuvant targeted therapy will be reviewed. Lastly, areas of future research will be highlighted.

Gramicidin A Blocks Tumor Growth and Angiogenesis through Inhibition of Hypoxia-Inducible Factor in Renal Cell Carcinoma

“…However, constitutive activation of HIF is also a characteristic of certain nonclear cell RCC subtypes (45)(46)(47)(48) even though VHL mutation is exceedingly rare in these tumors (49). Because VHL is functional in these subtypes, gramicidin A is likely to have therapeutic utility in this traditionally underserved patient population (8). Furthermore, gramicidin A may also prove effective in other cancers as upregulation of HIF occurs in the majority of solid tumors and generally correlates with poor survival (6).…”

“…are now routinely used for patients with ccRCC, and have succeeded in increasing progression-free survival and quality of life. However, these agents typically fail to achieve durable remission in most cases (7), and little is known about their utility for nonccRCC subtypes as these patients were excluded from clinical trials (8).…”

Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics

“…Sorafenib and sunitinib, which are broad-spectrum inhibitors of receptor tyrosine kinases (RTK) activated by HIF1 targets such as VEGF, PDGF, and TGFa, have been used in the treatment of sporadic papillary RCC with varying success. Somewhat more promising results have been obtained with mammalian target of rapamycin (mTOR) inhibitors [101]. Data about the specific response of HLRCC tumors to these molecules is unfortunately not available.…”

Collecting duct of Bellini renal carcinoma with psoas muscle recurrence: A case report and review of literature

“…This is congruent with other studies. 9 It seems natural that non-clear cell renal carcinoma takes on an alternate biochemical mechanism for tumour proliferation. Recent studies have suggested that the combination of gemcitabine and cisplatin provides an objectively good response for patients with CDC.…”