How Cancer Hijacks the Brain to Benefit Itself

In the last two centuries, complete treatments for many diseases, mostly infectious illnesses, have been discovered. The therapeutic targets for these diseases were clear and distinct from body cells. Therefore, targeting these pathogens had no adverse effects on the body. However, despite significant efforts to find new medications for cancer treatment, these therapeutic agents often result in large amounts of side effects. It appears that cancer cells are part of our body, and fighting cancer is essentially fighting against the body itself. Therefore, the body resists these treatments to neutralize the effects of therapeutic methods.

Natural anticancer mechanisms of the body are bypassed by cancer

The body has physiological mechanisms to prevent cancer formation. At the cellular level, tumor suppressors effectively hinder neoplastic alterations. At the systemic level, the tumor microenvironment, including proteins involved in extracellular skeleton and neighboring stromal cells, prevents the transformation of cells into a cancerous state. The immune system is also the most potent anti-cancer system that effectively removes and destroys cancer cells at early stages. However, if cancer cells grow beyond a certain threshold, they can evade the normal immune response to tumors.

When cancer size crosses a threshold, they can evade the normal anti-cancer mechanisms and also utilize the body's systems to keep themselves and grow more aggressively. Several mechanisms are suggested for these normal systems that are hired by tumors. While normal cells that detach from normal extracellular framework easily die, cancer cells possess tools that allow them to detach from the extracellular matrix and migrate to neighboring or distant tissues. Additionally, tumor cells prompt neighboring stromal cells such as endothelial cells or fibroblasts to generate new blood vessels and facilitate their growth and migration.

Interestingly, cancer cells can manipulate the immune system to promote their growth and development. While immune cells are designed to fight off infections and remove abnormal cells, cancer cells can escape these defenses. They can release chemical compounds that suppress the activity of immune cells, preventing them from recognizing and attacking the tumor cells. Cancer cells can produce proteins that make them invisible to immune cells, allowing them to escape detection. Some immune cells, like macrophages, can be tricked by cancer cells into aiding in tumor growth, angiogenesis (formation of new blood vessels), and migration to other tissues. While some types of T cells destroy cancerous cells, others help in further development [1]. Therefore, cancer along with its development not only neutralizes the defense systems but also recruits them to work for itself.

Interaction between cancer and the nervous system

The nervous system controls movement and sensory perception and also supplies nerve connections to tissue stem cell microenvironments. This implies the role of the central nervous system in tissue development, maintenance, and repair. The nervous system also interacts with tumor cells reciprocally. Nerves can both promote and suppress cancer growth. For instance, it has been shown that the sympathetic nervous system (SNS) has been shown to accelerate breast cancer growth and progression, while parasympathetic nerves (PNS) have been observed to reduce breast cancer growth and progression. The SNS can influence tumor growth and metastasis. Studies suggest that the SNS, through the release of norepinephrine, can activate beta-adrenergic signaling pathways, which can lead to increased tumor cell proliferation, formation of new blood vessels, and metastasis. These studies highlight the importance of stress in activating the SNS and promoting cancer progression. In advanced tumors, SNS innervation increases around tumor cells [2].

In contrast, cancer cells stimulate the production of new nerves around them and increase neuronal excitability. Some types of cancer, such as head and neck cancer, prostate cancer, and colorectal cancer, tend to attack the space surrounding a nerve to spread to distant tissues. It is as if the nerves attract them.

These observations prompted some researchers to pay more attention to the interaction between cancer and the nervous system. In a recent article, Douglas Hanahan—along with Robert Weinberg, the first to identify hallmarks of cancer in a landmark paper published in 2000 and 2011—explores the intricate relationship between cancer biology and neuroscience. The article emphasizes how cancer cells can modify neuronal signaling and how the nervous system can affect tumor behavior. This two-way interaction is essential for comprehending tumor biology and creating new treatment approaches [3].

Recently, much attention has been drawn to the role of cancer in manipulating the nervous system to benefit itself. Like a parasite, cancer cells hijack the nervous system to evade the immune system, create new blood vessels, facilitate their migration, promote inflammation, and cause pain. This is an interesting example of tissues that apparently should be under the control of the nervous system, but they cleverly influence the commander-in-chief and consequently take over entire systems in the body. This reciprocal interplay between cancer and the nervous system indicates that new therapeutic strategies should consider the nervous system as an indirect target to get better treatment outcomes. Additionally, psychotherapeutic approaches including cognitive behavioral therapy, mindfulness-based cognitive therapy, and psychodynamic therapy aimed at reducing stress and anxiety in cancer patients may offer an advantage in conjunction with traditional medications.