Selective treatment of cancer can involve targeting cytotoxic molecules to neoplastic cells; or the development of strategies able to target phenomena that are unique to tumor progression. Immunotherapeutic approaches are good examples of the former. This field centers around antibody targeting of isotopes, toxins or chemotherapeutics to cancer cells thus supporting tumor regression that is devoid of the dose-limiting toxicity associated with the destruction of non-cancerous cells, most commonly, bone marrow cells. Despite the promise of this approach, various problems associated with antibody stability and tumor penetration have precluded the effective exploitation of immunotherapeutics in many solid cancers. Tumors depend on angiogenesis to survive, and so targeting the tumor vasculature represents a strategy that could selective destroy cancerous growths. One of the earliest examples of this approach involved the use of a polysaccharide isolated from the culture medium of Group B streptococcus (CM101), a microbe known to cause respiratory distress in neonates. This is thought to occur through it's binding to a receptor whose expression becomes repressed very shortly after birth. In 1993 it was shown that CM101 could inhibit tumor growth in mice suggesting that receptor expression is reinduced under neoplastic conditions. The mechanism of action was related to a destruction of tumor blood vessels subsequent to local perivascular inflammation. Following successful preclinical studies CM101 was tested in the clinic and out of 15 patients, 5 showed tumor reduction or stabilization. Vascular targeting agents have now emerged as an alternative to antibody delivery of chemotherapeutics. Dietmar Siemann, professor of radiation oncology in University of Florida's College of Medicine, is a leader in this field. Dr Siemann's group has shown, in collaboration with a number of global biotechs, that two vascular targeting agents, Antisoma's 5,6-dimethyl-xanthenone-4 acetic acid (DMXAA) and OXiGENE's combretastatin A-4 disodium phosphate are both able to selectively destroy tumor vasculature. Most recently this group has shown that both targeting agents are also able to enhance the anti-cancer activity of cisplatin such that this chemotherapy was toxic to tumor cells at doses that failed to cause bone marrow stem cell toxicity. Thus vascular targeting appears to be able to combine the ability to target chemotherapies to the tumor environment, with selective blockade of tumor specific phenomena

Link to journal abstract:

Adapted from Siemann et al, Int J Cancer 2002 May 1;99(1):1-6

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