Efficacy of anti-angiogenic treatment of tumors in old versus young mice

• Published in: Mechanisms of ageing and development Vol. 127; no. 4; pp. 398 - 409
• Main Authors: Kaptzan, Tatiana, Skutelsky, Ehud, Itzhaki, Orit, Sinai, Judith, Huszar, Monica, Siegal, Annette, Ben-Zvi, Ronen, Jossiphov, Joseph, Michowitz, Moshe, Schiby, Ginnete, Leibovici, Judith
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.04.2006; Elsevier Science
• Subjects: Age Factors; Age-adjusted tumor therapy; Aging; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Biological and medical sciences; Development. Metamorphosis. Moult. Ageing; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Lymphoma - drug therapy; Melanoma, Experimental - drug therapy; Mice; Mice, Inbred C57BL; Models, Statistical; Neoplasm Transplantation; Neoplasms - drug therapy; Neoplasms - therapy; Neovascularization, Pathologic; Time Factors; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Aging; Angiogenesis; Age-adjusted tumor therapy; Vertebrata; Senescence; Mammalia; Treatment; Mouse; Ageing; Rodentia; Tumor; Age
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2005.12.011

Cancer treatment in the older population, the most afflicted by the disease, is as yet, inefficient. A reduced aggressiveness of tumors is often observed in the elderly, implying the necessity for therapeutic modalities adjusted to age. A rational design of age-related cancer therapy could be based on the mechanisms of this phenomenon. It is suggested that, in addition to the patient's old age-specific health problems (which prohibit the use of the aggressive cancer treatments now in use), the age-related differential tumor biology (apparently beneficial to the old) should also be considered for the design of treatment modalities suitable for the aged. Based on one mechanism of the reduced aggressiveness of tumors in the old (age-dependent decreased angiogenesis), we compared the effect of an anti-angiogenic treatment in young and old mice. TNP-470 treatment resulted in an inhibitory effect on B16 melanoma in both young and old mice but the effect was more pronounced in old animals. Moreover, a high percentage of long-term surviving animals was observed only in the old-treated mice. Treatment with TNP-470 of the AKR lymphoma produced similar results. We thus found a differential age-dependent therapeutic efficiency of an anti-angiogenic agent on two tumors. Importantly, the anti-angiogenic drug was more efficient against tumors of old animals.