Antiangiogenic Treatment of Hematological Tumors
Pp. 1-11 (11)
Domenico Ribatti, Vito Longo and Angelo Vacca
Antiangiogenesis was proposed as a cancer therapy over 20 years ago
and the list of compounds reported to possess antiangiogenic activity is extensive.
Inhibitors are grouped as specific and non-specific, depending on whether they
inhibit proliferation and/or migration of endothelial cells only or are also cytotoxic
for tumor cells. Antiangiogenic therapy is applicable to a wide variety of solid and
hematological tumors and there is evidence that tumors do not develop resistance
to its effects due to the low mutagenic potential of endothelial cells. It is too early
to predict whether antiangiogenesis will be of benefit in hematological malignancies.
Strategies that target both the stromal and tumor compartments, such as
combining traditional cytotoxic chemotherapy with antiangiogenic agents, may
indeed have an impact on drug resistance and improve the therapeutic response.
Conventional chemotherapeuticals used at very low doses, strikingly and reversibly
impact on certain endothelial cell functions without nonspecific cytotoxic or
necrotic damage. The use of low doses in “metronomic” chemotherapy (namely,
very frequent or continuous low-dose chemotherapy) as antiangiogenic targeting
strategy seem particularly effective against drug-resistant tumors, especially when
combined with a secondary antiangiogenic drug. Further studies are needed to
secure the comprehensive understanding and to elucidate the molecular basis of
the use of these new therapeutic approaches in the treatment of hematological
malignancies that actually are suboptimally treated with conventional cytotoxic
Angiogenesis, antiangiogenesis, hematological malignancies, tumor growth.
Department of Human Anatomy and Histology.