What Are Cancer Cells?-Our goal here is not to overwhelm you with information but rather to provide you with just the right basic information on cellular properties to enable you to answer the question "What are cancer cells?"; to understand how a cancer cell differs from a normal cell; and to give you a basis for understanding how the various proposed treatment options will act on your cancer.
You do not have to become a scientist or a geneticist but it is important to understand what cancer cells are and how cancer originates and progresses. You need to learn what normal cells are and how normal cells become cancer cells. We gave you a summary overview of this cancer information on our What Is Cancer and Learn About Cancer pages. Now it is time to fill in the details.
The references for the information in this section are given at the bottom of this webpage.
We all start as a single cell formed by the merger of a sperm and an egg. The fertilized egg divides and grows through several well defined stages to become an embryo. While all cells have same genetic information housed in their genes, as the embryo grows and develops various cells turn off certain genes and turn on others to become differentiated into the cells of your various organs such as lungs, liver, skin, brain, etc.
During the formation of the differentiated cells of each organ, different genes are expressed to enable the cells to be metabolically active to carry out the specific functions of the organ they comprise.
In addition to these differentiated functions, each normal cell within our organs retains certain growth control mechanisms that are essential for maintaining the healthy functioning of our organs and thus of our bodies.
A normal cell has all the inbuilt (genetic) regulation and feedback control systems to keep functional without growing and dividing in a manner that causes harm to its neighboring cells and the organ of which it is a part.
A normal cell becomes a cancer cell when a series of changes (mutations) in the DNA which cause changes in the genes which control the inbuilt regulation and control systems.
These control systems become damaged or inactivated in such a way that the cell exhibits one or more of the ten “Hallmarks of Cancer”. The table below summarizes the transformation of a normal cell into a cancer cell which exhibits all the “Hallmarks of Cancer”. The mutations are sequenced roughly in the order in which these capabilities are acquired by most cancers.
Cancer Hallmark #1 - Genome Instability: Acquisition of Hallmarks 2 through 10 depends in large part on a succession of alterations in the genomes of cancer cells. The extraordinary ability of genome maintenance systems to detect and resolve damage and defects in the DNA ensures that rates of spontaneous mutation are usually very low during each normal cell generation.
In the course of acquiring the roster of mutant genes needed to orchestrate tumorigenesis, represented here as Hallmarks 2 through 10, cancer cells often have increased the rates of mutation. This mutability, or genetic instability, is achieved through increased sensitivity to mutagenic agents and through a breakdown in one or several components of the genome maintenance machinery.
In addition, the accumulation of mutations can be accelerated by compromising the surveillance systems that normally monitor genomic integrity and normally force genetically damaged cells into either senescence or apoptosis (programmed cell death).
Cancer Hallmark #2 - Sustained Proliferative Signaling: The most fundamental trait of cancer cells involves their ability to sustain chronic proliferation (cell division). Normal tissues carefully control the production and release of growth-promoting signals such that cells only grow when they receive these growth-promoting signals. This growth is seldom required and rarely signaled in normal cells. Cancer cells, acquire the ability to grow independently of these external growth-promoting signals. They behave as if the growth-accelerator is stuck in the on position.
Cancer Hallmark #3 - Evasion of Anti-Growth Signaling: Normal cells have internal programs (anti-growth signaling) that “put the brakes on” limitless growth. In order to continue to proliferate, cancer cells must somehow evade anti-growth signals. In general, anti-growth signaling is mediated by the activation of tumor suppressor genes.
Dozens of tumor suppressors that operate in various ways to limit cell growth and proliferation have been discovered in various types of cancer cells. Cancer cells evade these Anti-growth signals when the products of Tumor-suppressor genes are inactivated by mutations thus removing the natural braking system from cell growth.
Cancer Hallmark #4 - Resistance to Apoptosis: The ability of tumor cell populations to expand in number is determined not only by the rate of cell proliferation but also by the rate of cell attrition. Programmed cell death, also known as apoptosis, represents a major source of this attrition.
In normal cells, the process of apoptosis naturally removes aged and damaged cells from the body. Cancer cells lose their ability to undergo apoptosis leading to uncontrolled cell proliferation and multiplication. Evasion of apoptosis may contribute to tumor development, progression, and also to treatment resistance.
Cancer Hallmark #5 - Replicative Immortality: Normal cells undergo a limited number of cell doublings after which growth stops and the cell dies. The normal cell accomplishes this control through a cell division counting devices (telomeres) on the ends of each chromosome.
Each cell division shortens the telomeres and when the telomeres reach a minimum length the cells stop growing (senescence) and cell death follows. When a mutation in the DNA of the normal cell occurs which turns on the production of a specific enzyme known as telomerase, this enzyme then prevents shortening of telomeres thus converting the normal cell to a cancer cell which now can carry out an unlimited number of cell doublings giving the cancer cells unlimited replicative potential or replicative immortality.
Cancer Hallmark #6 - Dysregulation of Metabolism: The chronic and often uncontrolled cell proliferation that represents the essence of cancer cells involves not only deregulated control of cell proliferation but also corresponding adjustments of energy metabolism in order to fuel rapid and extended cell growth and division.
Mutations leading to this deregulation of metabolism cause cancer cells to activate metabolic pathways which are less efficient in terms of glucose utilization but which will operate better in the low oxygen environment like a fast growing tumor. The result is that cancer cells have an abnormally high glucose utilization rate and the ability to tap into alternate energy pathways.
Cancer Hallmark #7 - Tumor-Promoting Inflammation: Pathologists have long recognized that some tumors are densely infiltrated by cells of the immune system. Inflammation is normally involved in stimulating cell growth leading to wound healing.
However, in cancer cells these healing mechanisms when amplified and extended can contribute to multiple hallmark capabilities by supplying bioactive molecules to the tumor microenvironment, including growth factors that sustain proliferative signaling, survival factors that limit cell death, proangiogenic factors, and extracellular matrix-modifying enzymes that facilitate angiogenesis, invasion, and metastasis.
Cancer Hallmark #8 - Immune System Evasion: Normal cells when damaged are targeted and killed by immune cells. Cancer cells are able to evade immune attack by several mechanisms including generation of regulatory cells and their secretions which ‘mask’ the cancer cells, defective antigen presentation and induction of immune suppressive mediators. As a result, cancer cells are not always effectively recognized and killed by immune cells.
Cancer Hallmark #9 - Angiogenesis: The oxygen and nutrients supplied by blood vessels are crucial for cell function and survival, obligating virtually all cells in a tissue to reside within 100 microns of a capillary blood vessel. During the formation of an organ, this closeness is ensured by coordinated growth of vessels. Once an organ is fully formed, the growth of new blood vessels (the process of angiogenesis) is carefully regulated.
Cancer cells in order to support their unlimited growth must develop the ability to grow new blood supply vessels. The ability to induce and sustain these new blood supply vessels (angiogenesis) seems to be acquired in a discrete step during tumor development, via an “angiogenic switch”. Tumors appear to activate the angiogenic switch by changing the balance of angiogenesis inducers and inhibitors through altered gene transcription.
Cancer Hallmark #10 - Tissue Invasion-Metastasis: Several classes of proteins involved in the tethering of cells to their surroundings in a tissue are altered via mutations in cells possessing invasive or metastatic capabilities.
The affected proteins include cell–cell adhesion molecules (CAMs) the modification of which ‘untether’ the cancer cells from their association with the tumor thus allowing migration of the cancer cells into the blood or lymph.
A second general characteristic of the invasive and metastatic capability involves extracellular proteases (protein hydrolyzing enzymes). Protease genes are up-regulated, protease inhibitor genes are down-regulated thus enabling the cancer cells to invade neighboring tissues.
The best way to capture and simplify how a normal cell becomes a cancer cell and how a cancer cell eventually becomes metastatic cancer is by incorporating all the above mutation driven cellular modifications into a narrative of a hypothetical journey of a cancer cell as it acquires the ten Hallmarks of Cancer.
A detailed account of this hypothetical journey is adapted and summarized in our Learn About Cancer page.
“The Hallmarks of Cancer”, Hanahan, Douglas and Robert A. Weinberg, Cell, v100, 57-100 (2000)
“Hallmarks of Cancer: The Next Generation”, Hanahan, Douglas and Robert A. Weinberg, Cell, v144, 646-674 (2011)
“Designing a Broad-Spectrum Integrated Approach for Cancer Prevention and Treatment”, Block, Keith, et al., Seminars in Cancer Biology, v35, 5276-5304 (2015)
“The Emperor of All Maladies – A Biography of Cancer”, a Pulitzer Prize-winning book by Siddharatha Mukherjeen, MD (2011)