Emotional Stress: Fueling Cancer Metastasis

The article has been co-authored by Tahreem Fiaz.

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Emotional stress is a state that tends to disturb the equilibrium between an individual’s physiology and its external environment. Any disturbance in the psychological attributes can haunt the physical fitness of the individual. Moreover, it can increase the susceptibility and course of many life-threatening diseases including cancer. Emotional imbalance is a common response of patients diagnosed with cancer. Furthermore, the adverse effects of cancer treatment and poor quality of life also contribute to an unbalanced mental state of the patients. Exposure to these disease-related factors can increase the risk of cancer metastasis (spreading of cancer cells to other organs). Studies based on animal models have shown that stress can promote the metastasis of cancer cells. According to a study published in Cancer Cell, stress-induced growth of pancreatic cancer cells has been observed in a socially isolated mice model as compared to the controls raised under normal conditions.

Understanding the biology of the stress response 

In general, there are two types of stress mechanisms: acute and chronic. Acute stress response is the body’s natural defense mechanism against threatening situations and is commonly known as the “fight or flight” mechanism.

Different regions of the brain can be activated to initiate a response in traumatic conditions. Amygdala, a set of neurons present in the medial temporal region of the brain, is involved in the perception and regulation of emotions. Whenever amygdala perceives a stressful stimulus, it sends a signal to the hypothalamus, which acts as a control center of our central nervous system. This communication further activates the sympathetic nervous system and release a hormone called adrenaline. The adrenaline rush in the body can recruit another response through Hypothalamic–pituitary–adrenal (HPA) axis. HPA-axis consists of three components — hypothalamus, pituitary and adrenal glands — that can trigger a cascade of hormones. This results in a high level of cortisol in the bloodstream.

When the stress stimulus disappears, the cortisol in the bloodstream acts as a feedback signal to hypothalamus and seizes the activity of stress-related pathways. This is a critical response to deal with such a situation and is associated with a feedback mechanism to stabilize the psychological state. 

On the other hand, consistent distress signals can lead to chronic conditions due to continuous HPA-axis activity. This is known as chronic stress response. It can affect and compromise various physiological processes including immune response and circadian rhythms. This results in the poor response of our natural defense mechanism against invading germs and inefficient brain performance.

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Source: Wikimedia

Cancer cells dissemination (Metastasis) from Primary region to other regions of the body (Source: National Cancer Institute, NIH)

How stress fuels cancer growth? 

Recent advancements in the field of psycho-oncology suggest a possible link between stress and cancer mortality. Patients diagnosed with cancer are predisposed to anxiety and depression due to constant mental pressure. Apart from the physical consequences of the treatment like chemotherapy, surgery and radiation, they continuously experience the ultimate threat of death. This situation will keep their HPA axis activity on the toe and contribute to several downstream outcomes including dysregulated gene expression and abnormal hormonal activity. This unfortunate coincidence of unbalanced brain activity during cancer acts as a fuel for the disease and contributes to its progression to the worst form: metastasis. 

Multiple factors, which are both genetic and environmental, are involved in the development of cancer. The amount of scientific evidence indicating the involvement of psychological stress in the onset of cancer is little, but it is nonetheless an active area of research nowadays.  Based on the available scientific facts, it is hard to say that stress can cause cancer, but recent evidence suggests that it can speed up the process of metastasis due to altered molecular signaling. 

Socio-economic pressure and poor quality of life can compromise the mental attributes of cancer patients. Importantly, women suffering from breast cancer are prone to chronic stress due to the loss of feminine characters like hair and breasts.   This can lead to social isolation and constant emotional pressure and over activation of their stress centers in the brain. The inefficient performance of the body lets the cancer cells to proliferate and metastasize.

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Source: Wikimedia

Hypothalamic–pituitary–adrenal (HPA) axis stimulatory pathway of cortisol release in Stress Condition

Stress can act as fuel for cancer cells due to the constant availability of stress hormones. The unnecessary presence of these hormones consumes resources at the disposal of normal cells by keeping them busy in dealing with a self-imposed threat. Moreover, it provides favorable conditions for the cancer cells to make changes and transform into a movable version to attack other organs in the body.

Chronic stress also affects the immune response and decreases the natural killer cell activity. One of the jobs of natural killer cells is to find and kill the cancer cell. The chances of killing a cancer cell on and after the time of its appearance are not enough and they become very low under a compromised immune system during persistent stress. The chemotherapeutic drugs not only kill the cancer cells but also decrease the number of immune cells. Stress adds insult to the injury and undermines the treatment outcomes.

Stress coping strategies for cancer patients 

A sound body and mind are essential for the overall well-being of cancer patients. Stress management is very important for cancer patients to promote their survival and quality of life. It is a supporting factor the rest of the people can provide to cancer patients to improve the chances of their survival and to decrease metastasis. 

Several strategies can help the patients to cope with emotional stress during cancer.  First, educate the patients and their families about the disease and the possible side effects of different types of treatments so it should not be a surprise for the patients and family members. Cancer is not contagious, so family and friends do not need to exhibit such behavior as may lead to the isolation of cancer patients. Ensure adequate quality time of the patients and their contribution in different activities. Take it as a disease, not as a curse, and help in maintaining a stress-free state of mind for the cancer patients to increase their likelihood of a quality living. Last but not least, give them hope not to despair.

The article has been co-authored by Tahreem Fiaz. Tahreem is currently pursuing M.Phil at Forman Christian College University Lahore

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