Renal cell carcinoma(RCC) is the most common form of kidney cancer and accounts for approximately 2% of adult cancers worldwide, with the highest incidence in North America and Western Europe. Prognosis is poor; five-year survival rates are less than 10% in stage IV patients.
Despite the identification of several genes involved in tumorigenesis, prognostic biomarkers to guide the use of RCC therapies are lacking. Investigation of the CAIX gene has shown elevated levels in patients who respond well to IL-2 therapy, but this treatment is used in only a small proportion of patients because of its toxicity.
The VHL gene is often mutated or silenced in clear-cell RCC, the most common form of RCC. Its downstream target, hypoxia-inducible factor (HIF), is central to tumor cells’ ability to promote angiogenesis and cell migration. Owing to increased understanding of this pathway, HIF-targeting proteins, as well as proteins acted on by HIF, are key drug targets. Drugs that target components of this pathway have been developed and approved for treatment of RCC, and we expect emerging agents that target this pathway to launch during our forecast period.
Multiple myeloma (myeloma), is a progressive hematologic disease that is both heterogeneous in nature and associated with numerous complications. It is difficult to treat with current therapies, such as the immunomodulatory drugs lenalidomide (Celgene’s Revlimid) and thalidomide (Celgene’s Thalidomide/Thalomid, Fujimoto Seiyaku’s Thaled) and the proteasome inhibitor bortezomib (Takeda/Janssen-Cilag/Janssen’s Velcade). As the search for more-effective treatments continues, identification of new pathways is urgently needed.
Histone deacetylase (HDAC) inhibitors offer a new method of treating myeloma through transcriptional activation and proliferative arrest or apoptosis of cancer cell lines. Although such drugs are unlikely to be used as monotherapies for myeloma, HDAC inhibitors in combination with current therapies will provide another treatment option for patients with recurrent and/or refractory disease.
Drugs that interfere with these pathways, such as perifosine (AEterna Zentaris/Keryx Biopharmaceuticals), could offer new approaches to treating myeloma.
Numerous therapies that target cell-surface molecules are in clinical development for myeloma. Few of these treatments will enjoy the same commercial success that some cell-surface-targeting agents have in other hematologic indications, but such drugs could hold the promise of providing targeted treatment to myeloma patients who overexpress specific cell-surface receptors or antigens.
Myeloma patients suffer from serious bone complications, such as bone pain and pathological fractures. Drugs that target processes that contribute to bone destruction may help to alleviate some of these painful and destructive complications by acting as supportive-care agents. The RANKL inhibitor denosumab (Amgen/GlaxoSmithKline/Daiichi Sankyo’s Prolia) is an exciting agent in development that could target these complications.