Skin blood, lymph vessels present new therapeutic target

Basic science research focusing on the role of the cutaneous vasculature in skin disease has provided new insights regarding pathogenesis and therapy, said Michael J. Detmar, M.D., delivering the Marion B. Sulzberger Memorial Award Lectureship yesterday.

As an example, Dr. Detmar noted that although investigations to elucidate the mechanisms for psoriasis development have predominantly focused on the role of the epidermis and the immune system, more recent evidence indicates the importance of the vascular system. Based on findings from a variety of animal and clinical studies conducted in his own laboratory and by other researchers, Dr. Detmar proposed that psoriasis develops over time as a result of upregulation of VEGF expression in the epidermis and the subsequent induction of angiogenesis. That theory is the basis for ongoing research to identify new targeted therapies for psoriasis acting to locally inhibit VEGF activity.

Research from Dr. Detmar and colleagues has also refuted the longstanding dogma that melanoma cells metastasize to the lymph nodes in a passive process wherein the tumor cells happen on pre-existing lymphatic vessels. Results from studies conducted so far suggest that melanomas can induce lymphatic vessel growth allowing for metastasis to sentinel lymph nodes. Once they reach the sentinel node, the tumor cells can again induce lymphangiogenesis leading to metastasis to more distant lymph nodes and finally to organs.

"Therefore, we would like to be able to block this induction of lymphatic vessel growth in order to prevent or inhibit melanoma metastasis, and initial experiments in animals suggest this might be possible," Dr. Detmar says.