Angiogenesis Inhibitors
When they learned about angiogenesis, scientists recognized a potential avenue for stopping the spread of cancer. The body makes chemicals that promote angiogenesis (growth of blood vessels) and other chemicals that stop it. Like most physiological processes, angiogenesis is subject to a feedback system. Doctors thought – if we can make the body’s anti-angiogenesis signal chemicals and supply it in excess to the patient, we can stop the growth of blood vessels in the body. And that would prevent the growth of tumors. Anti-angiogenesis therapy, also called angiogenesis inhibitor therapy, could theoretically be effective in fighting solid tumor cancer. It wouldn’t be relevant to leukemia and lymphomas but if the strategy worked on solid cancers, it would be a huge boon to oncology. (More than 80 percent of human cancers are solid tumors.)
The angiogenesis inhibitors could be those the body naturally makes – produced by genetic engineering techniques in the lab – or synthetic inhibitors. Either way, these inhibitors would be tested and proven as drugs. No angiogenesis inhibitor drugs existed yet, so it was a whole new category of anti-cancer medicines. There was a good deal of excitement in the 1990s about this approach to fighting cancer.
A flurry of activity by the pharmaceutical companies to develop these medicines followed. Bevacizumab, sold under the brand name Avastin, was the first drug of this class approved by the FDA. Several others followed. Disappointment followed as these did not turn out to be the wonder drugs people had hoped for. They show some efficacy (otherwise the FDA would not approve them), but they typically only add a few months to a patient’s life expectancy in clinical trials, and oncologists typically give them in conjunction with older style cytotoxic drugs.
However, antiangiogenesis drugs are part of the oncology medicine arsenal now. The Angiogenesis Foundation says the FDA has approved 13 drugs with “recognized antiangiogenic properties” for cancer. These include some monoclonal antibodies, some kinase inhibitors, and some mTOR inhibitors. Other cancer medicines have some antiangiogenesis including retinoids and hedgehog signaling inhibitors. At the molecular level, many kinase inhibitors work on the vascular endothelial growth factor which is one of the signals for blood vessel formation. You see drugs described as VEGF inhibitors.
Vascular Targeting Agents
For tumors that have already grown and have a blood vessel network, a tactic that might work is to attack those blood vessels and disable them. The blood vessel configuration in tumors is less orderly and effective than the vessels in normal tissue. Vascular Targeting Agents (VTA), also called Vascular Disrupting Agents (VDAs), induce ischemia, the process that is the culprit in many strokes and heart attacks. If it can be targeted, this ischemia can have benefits. One problem is that even if this process kills the tumor, malignant cells on the boundary between the tumor and the healthy tissue survive as they have access to blood vessels in the healthy tissue. VTAs as cancer therapeutics have not proven successful and none are approved for use.
Specific angiogenesis inhibitor cancer medicines
The National Cancer Institute lists the following as approved angiogenesis inhibitor drugs:
Lenalidomide
Thalidomide
Other medicines considered angiogenesis inhitors include Temsirolimus, Interferon, and Trifluridine/Tipiricil.
Details on some angiogenesis inhibitors not covered elsewhere:
Lenalidomide
Brand/Trade Names: Revlimid
Formula: C13H13N3O3
Manufacturers: Alembic Pharmaceuticals Limited, Apicore LLC, Aspire Lifesciences Pvt Ltd, Biocon Limited
Mechanism: Angiogenesis Inhibitor
Administration: Oral
Notes: Derivative of thalidomide. Approved by the FDA in 2005. Used for treatment of myelodysplastic syndrome, myeloma, and mantle cell lymphoma.
Pomalidomide
Brand/Trade Names: Pomalyst
Formula: C13H11N3O4
Manufacturers: Apicore LLC, Beijing Cooperate Pharmaceutical Co., Biocon Limited, Cipla
Mechanism: Angiogenesis Inhibitor
Administration: Oral
Notes: Derivative of thalidomide. Approved in the FDA in 2013. Used for treatment of myeloma.
Thalidomide
Brand/Trade Names: Thalomid, Immunoprin
Formula: C13H10N2O4
Manufacturers: Celgene Corporation, Aspire Lifesciences Pvt Ltd, Changzhou Pharmaceutical Factory, Hetero Drugs Limited
Mechanism: Angiogenesis Inhibitor
Administration: Oral
Notes: Approved for cancer treatment in 2006. Used for treatment of myeloma.