Recently, a series of shared molecular pathways have emerged that have in common a significant role in the pathogenesis and progression of both
atherosclerosis and
cancer. Oxidative stress and the cellular damage that results from it have been implicated in a wide variety of disease processes including
atherogenesis and
neoplasia. Toxic metabolites produced by cigarette smoking and increased
dietary fat intake are implicated in the pathogenesis of both diseases. It has been hypothesized that
atherosclerosis may begin when an injury or
infection mutates or transforms a single arterial smooth muscle cell in the progenitor of a proliferative clone similar to the most widely held theory of
carcinogenesis. Cell proliferation regulatory pathways including genes involved in the GIS checkpoint (p53, pRb, p15, p16, and
cyclins A, D, E, and cdk 2,4) have been associated with plaque progression,
stenosis and restenosis after angioplasty as well as in
cancer progression. Alterations in
cell adhesion molecules (
integrins,
cadherin-
catenins) have been linked to plaque formation and
thrombosis as well as to
tumor invasion and
metastasis. Altered expression of
proteases associated with thrombolysis has been implicated in
atherosclerotic plaque expansion and
hemorrhage and in the invasion and
metastasis of
malignancy.
Ligand-
growth factor receptor interactions (
tyrosine kinases) have been associated with early atherosclerotic lesions as well as
cancer development and spread. Nuclear
transcription factors such as NFkappaB have been associated with progression of both diseases.
Angiogenesis modulators have recently been linked to plaque expansion and restenosis of atherosclerotic lesions as well as local and metastatic
tumor expansion. Common disease treatments, such as the use of
growth factor inhibitors and
radiation treatment, established anticancer treatments, were recently introduced into
atherosclerosis therapeutic strategies to prevent restenosis after angioplasty and
endarterectomy. In conclusion, a series of molecular pathways of disease development and progression common to
atherosclerosis and
cancer support that the world's two most common diseases are far more closely aligned than previously believed and that emerging anti-inflammatory and antiproliferative therapeutic strategies may ultimately be efficacious in both conditions.