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Page 32 of 40 Maner et al. J Cancer Metastasis Treat 2020;6:37 I http://dx.doi.org/10.20517/2394-4722.2020.60

depending on their antigen priming, thus cancer cells may promote a change in lymphocyte DNA to avoid
[223]
recognizing the cells as foreign . There also will need to be consideration for the use of inactive mature
B- and T-lymphocytes that have not yet been presented with antigen compared to that of the lymphocytes
that have been presented with an antigen. It is possible that the human body is a state of active dynamic
mosaicism with genes turning on and off that have adapted genetic material to food products and other
antigens within the body. This information can ensure further accuracy when determining the somatic
genetics of patients with cutaneous malignancies and help with their treatment and prognosis.

Cellular electrical charges
Another important factor to consider with skin cancer genetics is that tumors tend to also have an electrical
charge as do many cells within the body. This is also a way to evade immune system attack. Tumor cells
are negatively charged. Lymphocytes that have been primed with tumor antigen are also negatively charge.
In the world of chemistry, similar charges are opposed to each other while opposite charges attract each
other. However, antibodies are positively charged. The positive charge of antibodies assists with T-helper
lymphocyte eradication of tumor cells. However, it is known that natural killer cells and CTLs are
important in immune killing of tumor cells, so there is more research that needs to be done in terms of the
effect of charge between immune cells and tumor cells as well as on genetic signaling.

Communication between immune system and nervous system
The central and peripheral nervous systems are important for regulating the systems in the body. In fact,
the nervous system directly affects the function of the immune system against fighting malignancies.
Chronic exposure to stressful events stimulates the adrenal gland, a neuroendocrine organ, to release
sympathetic nervous system stimulating hormones which disturbs the normal function and balance of the
immune system. In addition, this stress can also increase lymphatic vascularization in current tumors that
increases the number of chemokines release and promotes diapedesis of tumor cells. It is important to note
and follow patients who have chronic stressors without stress relief exercises to maintain homeostasis. This
neuroendocrine modulation also can influence the appearance of cutaneous tumors. As a result, decreasing
stressful events in the lives of patients can help prevent cutaneous malignancies from occurring [224] .

The body as a flux state
It is important to remember that tumors are not always a collection of cells that function the same way
undergoing the same processes at the same time. Many of these tumors function as organs, like that of
the heart or lungs with various cell types and cell functions. Likewise, there can be tumor cells that are
evading apoptosis by downregulating tumor suppressors, other cancer cells that are promoting cell growth
through the mutation of oncogenes while others are invading the stroma by damaging the underlying
adhesive molecules and releasing proteinases. In addition, cancer cells also can communicate amongst
each other with autocrine and paracrine signaling. This signaling can activate specific genetic pathways
to even mutate a normal, non-cancerous cell to that of a cancerous cell and change the genetic pathway
of those that are already malignant. All these processes can occur simultaneously especially in the faster
growing, more aggressive types of skin cancer. This hypothesis can explain why there are patients that
can go into complete remission from a treatment type and others are treatment resistant. The multiple
genetic signaling pathways activated, crosstalk and switching from one genetic pathway to another can be
the reason as to why there is treatment resistance. Tumor cells, like immune cells, may have an ability to
release chemokines leading to autocrine and paracrine communication between the cells. This process can
also form a communication system between the cells telling each of them their function and even invade
benign cells to become malignant. Adjuvant therapy might be considered in the earlier stages of cutaneous
malignancies depending on the number of genetic pathways that are discovered within these tumor cells.
These discoveries give providers further information to continuously perform full body skin examinations
and surveillance patient chronic inflammatory conditions for transformation into malignant conditions.