Cancer Pathways

Winding Our Way Down the Pathways of Cancer

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Cancer is an incredibly complex disease process that involves an enormous array and number of biochemical pathways, genes, signaling proteins and immune factors. Add to this the dizzying variety of cancer types, each idiosyncratically dependent upon specific features that activate each type and one can see why this disease is so difficult to treat let alone eradicate.

In a meager and admittedly simplified attempt to understand and possibly clarify the width and breadth of the cancer cascade, perhaps introducing and elucidating on some of the pathways that stimulate the formation of cancer and then some of the naturally occurring compounds that modulate these pathways may, to some degree, be helpful.

Vascular endothelial growth factor or VEGF is a signaling protein that’s primarily responsible for the stimulation of angiogenesis and vascularization or simply new blood vessel formation; for instance during embryonic development, after injury including stroke, in muscle tissue following intense exercise, and the formation of new venous and arterial structures to bypass blocked blood vessels. VEGF has also been associated with neuroprotective properties as well.

However, when VEGF is unregulated or over expressed, pathology can follow which can include the formation of solid cancerous tumors. In order for a tumor to grow it requires its own blood supply. VEGF therefore is integral in tumor proliferation, growth and metastasis, making it a potential target for various cancer therapeutics.

Another protein, high levels of which have also been implicated in the process of cancer generation is epidermal growth factor or EGF. EGF’s properties include cellular proliferation, differentiation, and survival.

EGF acts by binding to its cell receptor, epidermal growth factor receptor (EGFR) on the cell surface and then stimulating tyrosine kinase activity of the receptor.  Tyrosine kinase activity in turn initiates a cascade that results in a variety of biochemical changes within the cell that ultimately lead to DNA synthesis and cell proliferation.

In addition to the body manufacturing inappropriately high amounts of this growth factor, it can also develop altered forms of its cellular receptor that become abnormally active and consequently pathogenic.

It’s not surprising then, that Tyrosine kinase is being studied as a possible target for a variety of anti-cancer therapeutic drugs as its activity can initiate a variety of cellular functions including, in the case of cancer, unregulated cell growth.

Another kinase pathway is Mitogen activated protein kinases or MAPK. MAPKs are involved in directing cellular responses to a diverse array of stimuli including proinflammatory cytokines. They also, similar to the aforementioned signaling molecules, regulate cell proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis among other functions. MAPK is most relevant to breast cancer induction as estadiol, progesterone and testosterone can activate this particular pathway, stimulating cell proliferation.

Lastly, Nuclear factor-κβ(NF-κβ) is another protein complex that controls the transcription of DNA and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, and bacterial or viral antigens.  Inappropriate regulation of NF-κβ has been linked to a variety of cancers.

Not surprisingly, curcumin, which in past blogs I’ve called my favorite medicinal herb, modulates a variety of these pathways including VEGF, MAPK and NF-κβ making it a potentially profound anti-cancer compound as both a possible therapeutic and prophylactic agent.

The green tea extract EGCg is also a known pathway modulator by inhibiting the formation of VEGF and its effect on the cytokine interleukin-6.

Finally, grape seed extracts have been shown to be very effective against various cancer cell lines through induction of pathways such as caspase-3, a member of a family of proteins that help induce cell apoptosis.

The brief description of these pathways doesn’t even being to scratch the surface of the true complexity that is the cancer process but perhaps this will curry some interest and curiosity in pursuing additional information on this fascinating subject. As cancer has become so wide spread and ubiquitous, perhaps supplementation with these beneficial compounds should be considered an important part of our daily dietary regiment.

by Michael Fuhrman D.C.