is a rare and very
aggressive type of breast
cancer. It accounts for 1
to 5 percent of all breast
cancers diagnosed in the
Patients with ovarian
cancer that has
metastasized to distant
sites have a five-year
survival rate of around 30
percent ( 1).
several cancers. Leveraging our current knowledge of conventional chemotherapies and of the precision
targeting of anticancer antibodies to develop new antibody-drug conjugates not only improves patient
care by reducing side effects, but it also increases the return on prior investments in cancer research.
Blocking Tumor Sustenance
Research has shown that many solid tumors are very dependent on the growth of new blood
and lymphatic vessels to grow and survive. Thus, targeting these key components of the tumor
microenvironment provides an ideal avenue for therapy.
Since February 2004, the FDA has approved nine drugs that work in similar ways to impede the growth
of the new blood and lymphatic vessel networks that enable cancer cells to thrive (see Table 3, p. 16).
These drugs mainly function by stopping members of a family of growth-promoting proteins called VEGFs
from activating the molecules they attach to, VEGF receptors, which are mostly found on blood and
lymphatic vessel walls.
These therapies have had the biggest impact for patients with the most common type of kidney cancer
in adults, renal cell carcinoma. However, they also greatly benefit those with the most aggressive form
of liver cancer, as well as patients with some forms of pancreatic cancer; some gastrointestinal stromal
tumors and soft-tissue sarcomas; and some colorectal, lung, and thyroid cancers.
One new therapeutic option in this growing class of drugs is cabozantinib (Cometriq), which was
approved by the FDA for the treatment of metastatic thyroid cancer in November 2012 (136). In addition,
in September 2012, the FDA approved regorafenib (Stivarga) for the treatment of metastatic colorectal
cancer, after it was shown to significantly prolong patient survival (137). In light of the results of a large
trial that showed that regorafenib increased by more than fourfold the time before disease progressed for
patients with advanced gastrointestinal stromal tumors, the FDA approved regorafenib for the treatment
of this disease in February 2013 (138).
The nine FDA-approved drugs that block VEGFs or the function of VEGF receptors are currently being
tested in numerous clinical trials as treatments for several additional forms of cancer. One promising
clinical trial is examining the utility of pazopanib (Votrient) as a treatment for patients with advanced
ovarian cancer (139). Also encouraging are the initial results of a large trial testing sorafenib (Nexavar) as
a treatment for certain patients with thyroid cancer (140). Determining if treatments for certain cancers
might benefit other groups of patients not only improves patient care, but it also has the added bonus of
increasing the return on prior investments in cancer research.
In February 2013, the FDA approved Pomalidomide (Pomalyst) for the treatment of multiple myeloma.
Pomalidomide is a member of a family of drugs called immunomodulatory drugs. These drugs fight
multiple myeloma by modulating aspects of the immune system and by reducing the production of
VEGFs, which leads to disruption of new blood and lymphatic vessel networks (141). Importantly,