Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma

[Guest guest]

ls of Oncology, doi:10.1093/annonc/mdn666

Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma

J. Ruan1,*, K. Hajjar2, S. Rafii3 and J. P. Leonard1

1 Division of Hematology/Oncology, Department of Medicine, Center for Lymphoma

and Myeloma

2 Department of Cell and Developmental Biology

3 Department of Genetic Medicine, Weill Cornell Medical College and New

York-Presbyterian Hospital, USA

* Correspondence to: Dr J. Ruan, Division of Hematology/Oncology, Department of

Medicine, Center for Lymphoma and Myeloma, Weill Cornell Medical College, 1300

York Avenue, Room A-605A, NY 10065, USA. Tel: +1-212-746-2932; Fax:

+1-212-746-3844; E-mail: jruan@...

Angiogenesis, the growth of new blood vessels, requires dynamic expansion,

assembly and stabilization of vascular endothelial cells in response to

proangiogenic stimuli. Antiangiogenic strategies have become an important

therapeutic modality for solid tumors. While many aspects of postnatal

pathological angiogenesis have been extensively studied in the context of

nonhematopoietic neoplasms, the precise role of these processes in lymphoma

pathogenesis is under active investigation. Lymphoma growth and progression is

potentiated by at least two distinct angiogenic mechanisms: autocrine

stimulation of tumor cells via expression of vascular endothelial growth factor

(VEGF) and VEGF receptors by lymphoma cells, as well as paracrine influences of

proangiogenic tumor microenvironment on both local neovascular transformation

and recruitment of circulating bone marrow-derived progenitors.

Lymphoma-associated infiltrating host cells including hematopoietic monocytes, T

cells and mesenchymal pericytes have increasingly been associated with the

pathogenesis and prognosis of lymphoma, in part providing perivascular guidance

and support to neoangiogenesis. Collectively, these distinct angiogenic

mechanisms appear to be important therapeutic targets in selected non-Hodgkin's

lymphoma (NHL) subtypes. Understanding these pathways has led to the

introduction of antiangiogenic treatment strategies into the clinic where they

are currently under assessment in several ongoing studies of NHL patients.