Cancer happens when cells in our body have accumulated enough mutations to render them immune to regulating factors at the cellular environment. These cells will continue to divide, proliferate regardless of the state of cellular density of the environment they are in. Cancer cells also override the programmed cell – death protocol entitling them the status of immortality. These cells will continue to proliferate locally, depriving healthy cells of supply of blood and nutrients, translated into dysfunctional organ system.
Cancer cells at a certain point of mutation, will acquire the capability to trespass basal membrane allowing them to invade distant region of the body; a process called metastasis. They will repeat the same pattern at the distant area of the body, proliferate relentlessly, and perform angiogenesis to ensure ample supply of blood and nutrients to fuel their metabolic and mitotic activity. Distant, invaded healthy cells will also be deprived of blood and nutrients, compromising their function. All these events of cancer activity can be observed physically such as: a physical external abnormal mass due to the expanding mass of tumor cells, internal mass resulting in compression syndrome specific to location where they belong, such as pain, neurological deficit, etc, multi – organ failure, and wasting syndrome.
Tumor cells whether benign or malignant, result in abnormal growth of cells. If the tumor cells are located on the skin, or near the outer surface of the body, the mass can be observed as a lump, for example, breast lump, skin lump, etc. If the mass of tumor cells are located internally, and due to the non expandable nature of our inner compartments, the mass of tumor cells will manifest as compressive syndrome. This space occupying lesion will produce compression syndrome, for example, in brain tumor, the mass will compress certain region of the brain, pressing blood vessels, neurons, and other surrounding tissue. This will result in local neurological deficit. Healthy cells will be deprived of blood supply and will eventually die. If compression occurs at lungs, it will manifest as dyspnea; labored breathing. Compression at bone, for example in bone cancer, will result in deformed bone, and excruciating pain due to the stretching or pressing of the pain fibers in the periosteum, or the bone sheath.
Healthy cells will be in competition for blood supply and nutrients with cancer cells. Cancer cells are more active metabolically due to their continual cellular division activity. These cells will induce growth of blood vessels to them through a process called angiogenesis. This competition deprived the normal cells of nutrients, which will translate into organ dysfunction, reflected as clinical pathology abnormalities. Related markers of organ function will reflect abnormal value.
Since cancer cells are using up most of the cellular resources, the body will be undernourished rapidly, reported in cancer patients as rapid weight loss. Immune system will be compromised too, leaving the body vulnerable to diseases, and most importantly, also the body’s defenses against neoplastic cells. All of which greatly benefit the tumor cells.
75% of cancer related pain is attributed to the illness itself. Cancer related pain is primarily caused by the compression of surrounding tissue and nerve endings, sending pain signals to the brain. Inflammation due to dead cells may also trigger nociceptive pain. When the location of the tumor is superficial or near the surface of the body, the pain will be localized to the site, due to the dermatomal nature of pain nerve distribution. On the other hands, if the tumor affects visceral organs, pain is usually not accurately localized, and referred to other places distant from the original site. In some cases, general pain may be observed in patients with tumor in the central pain area of the brain. As pain is mostly related to the activity and size of the tumor cells, pain flare in patients may be associated with increasing tumor activity, but not all pain flare is due to increasing tumor activity.
Patients who are undergoing treatment such as radiation or chemotherapy may also experience post procedural pain, which is caused by the effect of radiation and chemotherapy on healthy cells. In that case, normal cells are damaged to a certain extent by the therapeutic process, resulting in pain from damaged neurons.
When cancer or healthy cells are injured in the therapeutic process, they release cytokines which serves as nociceptive stimulants to nerve endings, stimulating pain signals; a condition of sterile inflammation. That is the reason some people may experience pain post chemo or radiotherapy. With adequate analgesic, pain can usually be controlled well in 90 percent of the cases. It is important to notice that pain can be modulated by the patient’s perception and tolerance level, which explains why different people react differently to the same level of pain. In cancer patients, most of them are influenced by the stigma of impending doom and profound helplessness – depression is mostly observed in cancer patients – to an extent that it modulates their perception of pain.
Some patients do experience pain following courses of chemotherapy accompanied by increased surge of tumor markers. This phenomenon is not uncommon. While tumor markers rise usually correlates to increasing tumor activity, but it does not equate to inefficient chemotherapy. In many cases of proven efficient chemotherapy, cancer patients may register surge in tumor marker, accompanied by related symptoms such as pain. A study published by American Society of Clinical Oncology in 2003 on a group of patient with colorectal cancer, while In general, a rise in carcinoembryonic antigen (CEA) level in patients with metastatic colorectal cancer means tumor progression. They have, however, observed in four patients a transient increase in CEA level despite objective response among patients receiving oxaliplatin combination chemotherapy for metastatic colorectal cancer. Regardless of the sudden surge of tumor markers in some patients, but all patients shows declining tumor markers at the end of the chemotherapy course. It is the comparison of baseline and post chemotherapy level which is more important than the surge that happens during the course of the treatment.
Researchers are currently working to provide explanation of the phenomenon described above. Before the administration of chemotherapy, cancer cells are in equilibrium. Its growth is limited by the blood supply. As cancer cells growth rapidly, blood supply becomes the limiting factor, which they overcome by stimulating angiogenesis to supply nutrients to meet their metabolic demand. The mass of cells will continue to grow and the cells located at the core of the mass will slowly be deprived of blood supply, resulting in central necrosis, or death of the cells at the core of the tumor. Tumor mass will decrease in size, which will eventually provide more resources and room for growth. The cycle will continue, and in the process depriving the body of all its nutrients and energy.
When chemotherapy such as artemisinin is administered, some cancer cells died, releasing cytokines to stimulate pain nerve, and reduced cancer cells population will prompt increase in cancer cells turnover, resulting in increased level of tumor markers, and may exert the compression to the surrounding area to be registered as local or visceral pain. Once chemotherapy reaches the optimal level, that is when more cancer cells are destroyed than produced, which tilt the balance more towards cancer cells destruction. At this stage, symptoms may show improvement substantiated by the objective decline in tumor markers.