Therapy-induced stimulation of angiogenic molecules can promote
tumor angiogenesis leading to enhanced
tumor growth and
cancer metastasis. Several standard and emerging
therapies, such as radiation and
photodynamic therapy (
PDT), can induce angiogenic molecules, thus limiting their effectiveness.
PDT is approved for the treatment of several
cancers; however, its induction of
vascular endothelial growth factor (
VEGF) creates conditions favorable to enhanced
tumor growth and
metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative
PDT in an orthotopic model of
prostate cancer (LNCaP) increases not only
VEGF secretion (2.1-fold) but also the fraction of animals with
lymph node metastases.
PDT followed by administration of an
antiangiogenic agent,
TNP-470, abolished this increase and reduced local
tumor growth. On the other hand, administration of
TNP-470 before
PDT was less effective at local
tumor control. In addition, animals in all groups, except in the
PDT +
TNP-470 group, had a
weight loss of >3 g at the time of sacrifice; the weight of the animals in the
PDT +
TNP-470 group did not change. The significant reduction (P < 0.05) in
tumor weight and volume observed between the
PDT +
TNP-470 group and the control group suggests that the combination of
PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local
tumor growth and
metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes.