10.2.1 Primary tumor
TX
The primary tumor cannot be evaluated.
T0
There is no evidence of the primary tumor.
Tis
Carcinoma in situ (i.e., CIS) - that is, there are abnormal cells, but they have not yet spread to surrounding tissues.
Topic 10 Cancer
Cancer doesn’t refer to a kind of disease, but many diseases. There are more than 100 different types of cancer in total!
10.1 Locations and Classifications of Cancers
Location of a cancer
Most cancers are named for the organ or the cell type that they start from:
- As an example, colon cancer refers to cancer that begins from the colon.
- A carcinoma is a cancer that begins in the basal cells of the skin. Carcinomas include leukemia, astrocytomas, and melanomas.
Some main categories of cancer include the following:
Carcinomas
This is a cancer that begins in the skin or the tissues that line or cover internal organs.
Sarcoma
This is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or some other connective or supportive tissue.
Leukemia
This is cancer that starts in blood-forming tissues (e.g., bone marrow) and causes a large amount of abnormal blood cells to be produced and enter the blood.
Lymphoma and melanoma
These are kinds of cancers that begin in the cells of the immune system.
Central nervous system cancers
These are cancers that begin in the tissues of the brain and the spinal cord.
10.2 Stages of Cancer
Figure 10.1: Stages of Cancer
The TNM system (i.e., Tumor, Nodes, Metastasis) is widely used in most staging systems.
Figure 10.2: The TMN System of Classifying Lung Cancers
There are three main components to note in this system:
10.2.2 Regional Lymph Nodes
NX
Regional lymph nodes cannot be evaluated.
N0
Regional lymph nodes are not involved yet.
N1, N2, N3
Involvement of regional lymph nodes (each with an increasing amount of lymph nodes and / or extent of spread).
10.3 Cancers versus Tumors
Figure 10.3: Two Perspectives on a Cancer Cell
Figure 10.4: Physiology of a Tumor Cell
A cancer is a class of diseases that occur because of the uncontrolled cell growth of a group of cells. Cancers - by definition - are malignant.
A tumor is a swelling or a leision formed from the abnormal growth of cells,. A tumor can be:
Benign
In layman terms, non-cancerous. Benign tumors can be removed and in most cases, do not return. They also do not spread to other parts of the body.
Malignant tumors
These tumors are cancerous. Cells in these tumors invade nearby tissues and spread to other parts of the body.
10.3.1 Somatic Mutation Theory versus Tissue-Organizational Field Theory
There are two differences to note between both types of theories:
10.3.1.1 Somatic Mutation Theory (i.e., SMT)
SMT has been the prevailing paradigm in research
This theory states that all cancer cells come from a single somatic cell that has accumulated DNA mutations. Hence, cancer is a disease of cell proliferation caused by mutations in the genes that control proliferation and the cell cycle.
10.3.1.2 Tissue-Organizational Field Theory (i.e., TOFT)
TOFT proposes that cancer is tissue-based and not cell-based.
This theory assumes that proliferation is the default state of cells in multicellular organisms. Hence, proliferation of a tumor happens when these tissues are freed from the restrictions that are imposed by normal tissue organization.
Reversibility is central to this idea.
10.4 Ten Hallmarks of Cancer and Four Enabling Characteristics
Figure 10.5: Characteristics and Hallmarks of Cancer
The professor describes the above graphic in more detail below:
Sustaining proliferative signalling
This is the most fundamental trait of cancer - this also refers to oncogene mutation or activation
Evading growth suppressors
Tumor cells are insensitive to anti-growth signals and may have mutations in their tumor suppressor genes / proteins (e.g., p53, Rb).
Resisting cell death
Cancer cells are resistant to apoptosis - a hallmark of cancer cells!
The rate of proliferation and the rate of attrition determines the ability of a cancer cell to expand.
Enabling Replicative Immortality
Cancer cells have limitless replicative potential; telomere maintenance is evident in almost all types of malignant cells (i.e., 80% - 95% of cells).
Inducing or accessing vasculature
Cancer cells all require some form of sustenance in terms of nutrients and oxygen (and some ability to remove wastes).
This facilitates metastasis.
Activating invasion and metastasis
Figure 10.6: Activation of Invasion and Metastasis
This is the final the fatal stage of cancer and is a multi-step process.
Avoiding immune destruction
Cancer cells may paralyze infiltrating immune cells by secreting TGF-beta or other immunosuppresive factors.
Deregulating cellular energetics
Warburg effects occur here2. This is because metastasis needs fuel to happen.
Interestingly, the rate of glucose metabolism happens ten to 100 times faster than oxidative phosphorylation in glycolysis.
Tumor-promoting inflammation
The secretion of growth factors that induce proliferation, survival, angiogenesis, and metastasis.
Genome instability and mutation
Humor tumors have a large amount of genome mutations.
A mnemonic for remembering these ten ideas are: GREAT IDEAS.
10.5 Four New Hallmarks of Cancer
Figure 10.7: Four New Hallmarks of Cancer
The four new (recently discovered) hallmarks are:
Unlocking phenotypic plasticity
Phenotypic plasticity is the phenomenon where a given genotype differentiates into several groups of phenotypes in a given environment. In the context of cancer cells, this includes transdifferentiation into different cell lineages and the de-differentiation from mature to progenitor states.
Senescent cells
When a cell becomes senescent, this process is irreversible. Maintaining senescense is a mechanism for maintaining cell homeostasis.
Non-mutational epigenetic re-programming
The environment around a cell can contribute to its epigenetics.
Polymorphic microbiomes
Microbiomes also have a profound effect on disease and health (e.g., probiotics and pathogens). Some microbiomes can have positive effects on human health whereas others don’t.
However, possible mechanisms for microbiome inlfuence on human health are still being developed.
This is the observation that tumor cells use glycolysis instead of oxidative phosphorylation for energy production.↩︎