The traditional view has been, and to a large extent still is, that cancer is a genetic disease, with its origin and treatment based on damaged “hardware”, implying the genetic material inside the human cell. However, research over the past decade has indicated that cancer may well be a “software” disease, based on the incorrect functioning of the biochemical processes taking place inside the cell. These findings offer new treatment possibilities in future, based on altering the biochemical processes taking place inside the cell, instead of the traditional approach of killing the whole cancerous cell with chemotherapy or radiation. To make sense of the “hardware” or “software” approaches, one needs to look closer at what exactly takes place inside the human cell.
The life cycle of human cells:
The human body is made up of an estimated 30 trillion cells of many different types, such as cells of the skin, internal organs, muscle tissue, bones, and the brain, that all look different and have different functions.
Human cells grow into maturity to carry out their functions in the body, with the ability to divide to form new cells when needed to replace damaged or aging cells. The old or damaged cells undergo a process of programmed cell death or apoptosis, being replaced by new cells. A normal cell has a life cycle of growth, maturity, division, and death (apoptosis).
On average cells are replaced every 7 – 10 years, but cells in different organs vary in lifespan. This ranges from neutrophils (making up 50-70% of white blood cells) that might last for 4 hours or less; sperm cells have a lifespan of only 3 days; while brain cells in the cerebral cortex, like the cells in the middle of the lens of the eye, last a lifetime. Cells that have died off on the surface of the body or in the lining of the gut are sloughed off and discarded, while those inside our bodies gets scavenged by a type of white blood cell called phagocytes that ingest the dead cells.
Inside the human cell:
The human body is the sum of trillions of cells, which are organized into more than 200 major types. Each of these cells are highly active with general routine duties such as creating and using energy, manufacturing protein molecules for running cellular processes, and responding to input from the environment, while also having specific duties, depending on the type of cell, such as building bone or making hormones.
Live Science provides an overview on how cells function. Inside the cell are several cellular compartments, called organelles, each within its own membrane.
- The cell membrane encapsulates every cell and protects the cell’s internal environment. The cell membrane is the gatekeeper for anything that enters or leaves the cell, while acting as a barrier to maintain the internal composition of the cell. Some proteins in the membrane act as receptors which sense the cell’s external environment, and then send chemical signals to the interior of the cell. Other proteins in the membrane acts as transporters that regulate the entry or exit of substances in and out of the cell.
- Apart from various organelles, about 50% of the cell is filled with cytosol, which is a thick brew made of water, salts, nutrients, and proteins. The simple sugar glucose is broken down in the cytosol.
- The nucleus is an organelle that occupies about 10% of the cell’s interior and contains the cell’s genetic material (DNA), which is the blueprint for the manufacturing of billions of protein molecules, which are involved in virtually every cellular process. The DNA, for example, tells a cell: “You are a brain cell, produce the necessary proteins to grow branching dendrites to receive information from other brain cells and grow an axion to send signals to other brain cells. You are an information messenger, using electrical and chemical signals to transmit information between different areas in the brain.”
- Next to the nucleus are two types of large, interconnected sacs – the endoplasmic reticulum. One type is covered in ribosomes that make proteins, while the other type makes lipids (fats) and breaks down toxic molecules.
- The newly made proteins and lipids are sent to other organelles – the Golgi complex – where they are processed and sent to their final destinations, inside or outside the cell.
- The energy giving “batteries” of cells are organelles called mitochondria, (singular mitochondrion) where energy from food gets converted and stored in a small molecule called adenosine triphosphate (ATP), which provides the energy for other biochemical reactions in the cell. On average a typical cell burns through about 1 billion molecules of ATP every 1 to 2 minutes. Mitochondria have an outer membrane, which encapsulates these organelles, while the inner membrane has an increased surface area in aid of the production of ATP, due to folds (cristae) that extend into the center of the mitochondria.
- Lysosomes contain digestive enzymes that are involved in intracellular metabolism.
- Ribosomes are involved in the translation of genetic information (mRNA) from the DNA in the cell nucleus. They interpret the message carried by mRNA and then produce the specific protein. Ribosomes are the protein producing factories in cells.
The metabolic processes taking place in the cell, in a nutshell, means that biochemical energy is harvested from organic, digested end products from the food we eat, for example glucose from carbohydrates, and then stored in energy-carrying biomolecules (ATP), to be used in the activities in the cell that require energy. Depending on the type of cell and its function, different cells have different numbers of mitochondria, depending on the specific energy needs of the type of cell. For example, more mitochondria are found in cells of the liver, the kidneys, the muscles and the brain. Mitochondria are of particular interest in the latest cancer research, as defects in the energy generating pathways of the mitochondria can lead to many different types of symptoms in the body.
Cell division: The cells in the body divide by each parent cell dividing into two identical daughter cells, and this process is repeated over time. Cells regulate their division by using chemical signals to communicate with each other. Not all cells divide at the same rate, as some cells such as skin cells reproduce at a higher rate due to the daily loss of these cells with continual contact with the external environment. Other types of cells in the brain, nervous system, and various organs divide less often, as these types of cells do not die as fast. On average the human body loses an estimated 50 million cells per day, which are replenished through cell division. Cell division is of particular interest in the study of cancer, as cells that keep on dividing, after they should have stopped, form cancerous cells.
What is cancer?
Cancer refers to any malignant growth or tumor in the body, caused by abnormal and uncontrolled cell growth in that area. Cells are constantly renewing themselves, but when they get damaged in some way, the normal regular division of cells – with new cells forming and old ones dying off – goes haywire and cells in the affected area continue to divide and grow uncontrollably, while they can also invade surrounding tissue or spread to other areas in the body, known as metastases.
Malfunctions in the cell’s regulatory mechanisms leads to the abnormal growth of cells. The uncontrolled growth of abnormal cells in the body may form tumors.
- Tumours that are localized and pose little risk to health are called benign.
- Tumours that aggressively grow, invade surrounding tissue, and spread to distant sites aggressively are designated malignant.
Not all the cells within a malignant tumor are able to spread and seed elsewhere, as the cells derive from a single cell. Only some of the cells from successive divisions develop the genetic alterations that would allow the cell to seed other tissue. One school of thought is that metastases is actually driven by the macrophages of the Immune system. Macrophages are able to move in and out of blood vessels, and by fusing with cancer cells, they enable metastases. Once these tumor cells break away from the parent tumor and end up in the blood stream, they eventually lodge in the capillaries of other organs and exit into those organs, where they grow and form new tumors.
Traditional theory – cancer is a genetic disease:
The traditional view that cancer is a genetic disease, says cancer is caused by certain changes to the genes that control the way our cells’ function, grow, and divide. These gene changes can cause cells to evade normal growth controls, such as increasing the production of a protein that makes cells grow. Genetic changes or mutations that cause cancer can also result from errors that occur as cells divide. Abnormal signaling in the cell from both oncogenes (a gene that can become permanently activated and cause the cell to divide out of control) and tumour suppressor genes (genes that normally slows down cell division and which may become inactivated, resulting in uncontrolled cell division). This abnormal signaling may cause resistance to the normal programmed and controlled death of cells. All of these genetic mutations may result in uncontrolled cell growth and contribute to the development of multiple types of human cancers. Theory has it that cancer cells have more genetic mutations than normal cells and these changes may be the cause of cancer.
The view that cancer is a genetic disease differs from inherited mutations. Some people may inherit mutations in certain genes that result in a predisposition to develop certain cancers, but these inherited genetic mutations (eg BRCA 1, 11) only play a major role in about 5 to 10 percent of all cancers. Not everybody who inherit a cancer-predisposing mutation will necessarily develop cancer.
Recent theory – cancer is a mitochondrial metabolic disease:
Metabolism refers to the way cells use carbohydrates, fats, and proteins from food to produce the energy that cells need to grow, reproduce via cell division, and stay healthy.
The shift in thinking – from viewing cancer as a genetic disease to viewing cancer as a mitochondrial metabolic disorder – mostly occurred during the last decade, with more of the latest research supporting this thinking. Research has shown that the energy metabolism of tumor cells varies greatly from normal cells. The most common structural problem in most cancer cells are abnormal (eg no cristae) or dysfunctional mitochondria. Tumor cells show elevated glucose consumption with the production of high levels of lactate. Dysfunctional mitochondria prevent the normal aerobic production of ATP in cancer cells, and hence their switch to aerobic fermentation of glucose in the cytosol, leading to lactate production. Another source of ATP production for cancer cells, is the amino acid, glutamine, which provides ATP through substrate level phosphorylation in the damaged mitochondria. The thinking is that many cancers could regress, or be prevented, if these energy sources are restricted.
Emerging evidence from research is consistent with the notion that impaired mitochondrial function seems to be at the root of the development of cancerous cells, as mitochondrial dysfunction has been observed in a wide spectrum of human cancers. Cancer is deemed to originate from damage to the mitochondria (and its DNA), which leads to ROS (reactive oxygen species) production in these vital organellae, which, in turn leads to genetic mutations to the DNA in the nucleus of the cell.
Conclusions:
A clear understanding of the origins of cancer is the foundation on which to build successful strategies for cancer prevention and treatment. Viewing cancer as a mitochondrial metabolic disease offers the possibility of a different approach to cancer treatment. While traditional cancer treatment such as chemotherapy and radiation are aimed at killing cancer cells (with serious side effects to the body), the metabolic approach aims to keep cancer cells from growing by changing or slowing their metabolism, through restricting their energy sources as much as possible. All normal cells in the body will survive by increasing ketone levels in the bloodstream, through a ketogenic diet, which will then serve as their main energy source. However, damaged or dysfunctional mitochondria are not able to metabolize ketones, and thus this energy source is not available to cancer cells.
In essence, the genetic mutations to the oncogenes and tumor suppressor genes in the DNA of tumour cells, could likely be the downstream effect of damaged and dysfunctional mitochondria
Research in this regard is still in the early stages, although very promising, with the focus on finding new ways to hamper cancer cell metabolism, in which the tumor cells will eventually shrink and die.
References:
Metabolic disease. Published online Encyclopedia Britannica. (www.britannica.com)
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The genetics of cancer. Published online and updated 12 October 2017. National Cancer Institute. (USA). (www.cancer.gov)
Cancer genetics overview. Published online and updated 17 March 2021. National Cancer Institute. (USA). (www.cancer.gov)
Is cancer a genetic disease or a metabolic disease? Published 23 May 2015. E Bio Medicine. (Journal.) National Center for Biotechnology Information. US National Library for Medicine. National Institutes of Health. (www.ncbi.nlm.nih.gov)
Is cancer a metabolic disorder? Published online and updated 1 July 2019. News Medical Life Sciences. (www.news-medical.net)
Cancer etiology: A metabolic disease originating from life’s major evolutionary transition? Published 8 October 2019. Oxidative Medicine and Cellular Longevity. (Peer review journal.) Hindawi. (An open access journal publisher.) (www.hindawi.com)
Cancer as a mitochondrial metabolic disease. Published 7 July 2015. Frontiers in cell and developmental Biology. (www.frontiersin.org)
What is cancer metabolism? Published 21 July 2020. WebMD. (www.webmd.com)
Understanding cancer – the basics. Published 24 January 2020. WebMD. (www.webmd.com)
Is cancer a genetic or metabolic disease? Published 20 January 2019. CrossFit. (www.crossfit.com)
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