Cancer Module Summary
CANCER AND CANCER TERMINOLOGY
Cancer – uncontrolled growth of abnormal cells in the body; other terms: malignant or malignancy
Malignant or cancerous cells – composed of less well-differentiated cells that have lost the ability to
control both cell proliferation and differentiation into a mature cell
Oncology – study of tumors and their treatment including non-malignant or benign tumors
INCIDENCE AND MORTALITY RATES
Risk of cancer increases with age – with a higher % of cancer cases occurring in those 70 or older.
More specifically, prostate cancer is the most common cancers among Canadian men and breast cancer
is the most common cancer types among Canadian women in Canada.
In terms of estimated deaths, lung cancer is the leading cause of cancer death for both men and women,
followed by colorectal cancer in men and breast cancer in women.
CELL CYCLE AND CARCINOGENESIS
Cell cycle – sequence of events involved in replication and distribution of DNA to daughter cells in which
a starting cell duplicates its contents and divides into two identical daughter cells
Five phases of the cell cycle G zero, G1, S, G2, and M
Two major phases of cell cycle synthesis or S phase (DNA is synthesized and chromosomes are
replicated) and mitosis or M phase (cell divides and 2 daughter cells are formed).
The G phases are when the cell is metabolically active or growing enzymes or proteins in preparation for
DNA synthesis or mitotic division.
After mitosis daughter cells either go into a state of dormancy called the G zero phase (not actively
proliferating) or the cell enters the G1 phase to begin the cell reproductive cycle again
Duration of the M, G2 and S phases is relatively constant, but G1 phase varies from hours to days. This
determines the overall length of the cell cycle.
Differentiation & Proliferation
Cells duplicate (and divide) increase in number of cells resulting daughter cells organize and
become differentiated. Cell differentiation is where proliferating cells become specialized.
This is an orderly process, with increasing specialization occurring with each step.
3 main categories of cells produced through cell differentiation and proliferation cells that never or
rarely divide (ex. nerve cells), cells that continue to proliferate and then die, and stem cells which enter
the cell cycle and produce progenitor cells when required.
Progenitor cells are early descendants of stem cells that can differentiate to form one or more kinds of
cells but cannot divide and reproduce indefinitely (more limited in the kinds of cells it can become).
Stem cells can remain quiet until needed and then be called upon to produce daughter cells of the type
required (it is a cell from which other types of cells develop).
Cancer cells are able to complete the cell cycle more quickly by decreasing the length of time spent in
the G1 phase. They are also much less likely to enter or remain in the G zero phase of the cell cycle.
Several checkpoints in cell cycle allow cycle to be stopped if previous events weren’t completed.
Example G1-5 checkpoint monitors whether the DNA in the chromosomes is damaged by radiation or
chemicals, and the G2 M checkpoint prevents entry into mitosis if DNA replication is not complete.
Transition from G2 to M is believed to be one of the most important checkpoints in the cell cycle.
Normal cells in the body follow an orderly path of growth, division, and death. A series of complex
molecular processes are used to keep these cells growing in controlled and programmed fashion. Carcinogenesis process by which normal cells are transformed into cancer cells, caused by a mutation
of the genetic material of normal cells (upsets normal balance between proliferation and cell death)
results in uncontrolled cell division and tumor development in the body.
Normal cells undergo a finite number of divisions before they stop completely, cancer cells have the
capacity to undergo infinite number of cell divisions.
All cancer is genetic, in that it is triggered by altered genes. Genes that control the orderly replication of
cells become damaged, allowing the cells to reproduce without restraint.
Cancer disease in which a single normal body cell undergoes a genetic transformation into a cancer
cell. This cell and its descendants produce the population of cells that we recognize as a tumor.
Carcinogenesis process in which normal cells become cancer cells. Three stages of this process: 1)
initiation, 2) promotion, and 3) progression.
Initiation exposure of cells to appropriate doses of carcinogenic agent (ex. chemicals, physical, or
biological and produce irreversible changes) that makes them susceptible to malignant transformation.
Promotion unregulated and accelerated growth of the mutated cells. Dysplasia – abnormality of cell
development during the promotion stage, often indicative of an early neoplastic process.
Progression process in which tumor cells acquire malignant changes and autonomous growth
tendencies that promote invasiveness and metastatic capabilities.
Carcinoma in situ transformation of a neoplastic lesion to one in which cells undergo no maturation
so may be considered cancer like. Remains localized, hasn’t invaded past the basement membrane.
Invasive carcinoma is the final step in this sequence which is cancer that has invaded beyond the
basement membrane and has the potential to metastasize or spread to other parts of the body.
Gene and DNA Structure
Genes reside within chromosomes, the large DNA molecules, which are composed of two chemical
strands twisted around each other to form a “double helix”.
Each strand is constructed from millions of chemical building blocks called “bases”.
DNA contains four different bases: adenine (A), thymine (T), cytosine (C), and guanine (G).
The sequential order of the bases in any given gene determines the message the gene contains.
How does it occur?
In their normal forms, genes control the cell cycle, the sequence of events by which cells enlarge and
divide. The cell division process is dependent on a tightly controlled sequence of events.
When this process does not occur properly, unregulated cell growth may be the end result.
Of the genes that exist, there is a small subset that seem to be particularly important in the initiation,
promotion, and progression of all different kinds of cancer.
Two broad categories of genes that have been identified: proto-oncogene and tumor suppressor genes
Proto-oncogenes encourage cell division and tumor suppressor genes inhibit cell division. Together, they
coordinate the regulated growth that normally ensures that each tissue/organ in the body maintain a
size and structure that meet the body’s needs.
Mutated proto oncogenes become oncogenes, genes that stimulate excessive division. Mutations in
tumor suppressor genes inactivate these genes, eliminating the critical inhibition of cell division that
normally prevents excessive growth. Mutations in these two categories of genes account for much of the
uncontrolled cell division that occurs in human cancers.
Oncogenes result from the activation or turning on of proto-oncogenes but tumor suppressor genes
cause cancer when they are inactivated or turned off.
Proto-Oncogenes and Oncogenes
Proto-oncogenes encourage normal cell division and when they become mutated, they are oncogenes. Oncogenes can contribute to the development of cancer by instructing cells to make proteins or “go
signals” that stimulate excessive cell growth and division. This causes a cell’s growth-signalling pathway
to become hyperactive. This causes the cell to continually grow and divide.
Most cancer causing mutations involving oncogenes are acquired, not inherited.
Tumor Suppressor Genes
Tumor suppressor genes play a critical role in regulating when cells are allowed to divide and increase
in number. When DNA damage is detected in a cell, some tumor suppressor genes can send “stop
signals” to the cell to stop it from multiplying until the damage is repaired.
When they don’t function correctly, cells with DNA damage continue to divide and can accumulate
further DNA damage that can lead to a cells to grow and divide in an uncontrolled fashion.
Individuals who inherit an increased risk of developing cancer often are born with one defective copy of
a tumor suppressor gene. This will not cause cancer though because the other normal copy is still
functional. But if the second copy undergoes mutation then the person may develop cancer.
DNA Sequencing Gone Wrong
The DNA repair system also helps cells avoid runaway cell division by instructing a cell to repair damaged
DNA. This system operates in every cell in the body, detecting and correcting errors in DNA.
Mutations in the DNA repair system can occur in several different ways.
Simplest type of mutation a change in a single base along the base sequence of a particular gene
In other cases, one or more bases may be added or deleted. And sometimes, large segments of a DNA
molecule are accidentally repeated, deleted, or moved.
Errors also occur during DNA replication. In most cases, such errors are rapidly corrected by the cell’s
DNA repair system however, mutations in this DNA repair system can lead to a failure in repair, which in
turn allows subsequent mutations to become a permanent feature in that cell and its descendants.
DNA polymerase copies both strands of the DNA – the top strand and the bottom strand.
Normally there is going to be an A opposite a T, and C opposite a G, but suppose it makes a mistake and
copies a T where a C should be. That mistake is a potential mutation.
Fortunately cells have repair systems that can erase those mutations. These repair proteins recruit
another enzyme called EXO1 – an exonuclease that chops off the mutant strand. This allows a DNA
polymerase to come by and synthesize the correct strand, fixing up the DNA and making it normal.
This is another system that works in our body to balance the generation of new cells via cell division and
the loss of cells through cell death. Old cells become damaged over time and are eliminated by a process
termed programmed cell death or apoptosis.
Specific tumor suppressor genes can stimulate cells with damaged DNA to commit “cell suicide.”
In cells that have undergone DNA damage, the tumor suppressor p53 protein, initiates cells suicide,
thereby preventing the genetically damaged cell from growing out of control. In a cell with a mutated
p53 gene, cell suicide system is defective, and the damaged cell goes on in the cell cycle and divides.
NK Cell & the Immune System
The immune system and natural killer cells is another back up system that affects the way cancer grows.
The immune system is the first and last defence against cancer. NK cells are a part of the immune system
and are very important because they can target tumors and cancer cells and kill them.
A number of chemotherapeutic drugs need the immune system to be intact for the drugs to be effective.
Over 10,000 times each day our immune system destroys cells that could become cancerous.
Tumor cells progress from a state of initiation to promotion to progression and finally metastasis.
The spread of cancer from its original location to other parts of the body is called metastasis. This is a
critical event in cancer. Metastasis can occur in two ways. Firstly, malignant cells can directly invade or extend into adjacent organs or sites. Secondly, individual
cancer cells may move away from the primary tumor and enter the blood or lymph circulation.
Once tumor cells have successfully entered the blood and lymph circulation, they travel and get stuck in
the capillary bed of a distant organ or site. They can continue to grow here until they burst.
The most common sites of cancer metastasis are the lungs, bones, and liver.
Angiogenesis is the process of forming new blood vessels which is needed for cancer metastasis. It
begins when a tumor becomes large enough where it needs to increase the supply of nutrients and
oxygen it receives.
Hypoxia triggers the tumor and its surrounding environment to release signals that result in the growth
of blood vessels towards and into the tumor. These new vessels supply oxygen and nutrients that allow
the tumor to continue growing.
Normal Cell Angiogenesis
Angiogenesis occurs normally in the human body at specific times in development and growth.
For example, a developing child in a mother’s womb must create the vast network of arteries, veins, and
capillaries that are found in the human body.
Also, angiogenesis is necessary for the repair or regeneration of tissue during wound healing.
Tumor Cell Angiogenesis
Tumor angiogenesis is the proliferation of a network of blood vessels that penetrate into cancerous
growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis begins with
cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue.
This signalling activates certain genes in the host tissue that make proteins to encourage growth of new
blood vessels. In a study, they found that without angiogenesis, tumor growth stopped.
Researchers are now asking if inhibiting angiogenesis can slow down or prevent the growth and spread
of cancer cells in humans. Angiogenesis inhibitors are currently being tested in cancer patients.
One class of angiogenesis inhibitors being tested in cancer patients are molecules that directly inhibit
the growth of endothelial cells.
A second group of angiogenesis inhibitors being tested in human clinical trials are molecules that
interfere with steps in the angiogenesis signalling cascade.
Avastin (a drug in this category) is the first to be FDA approved and has been proven to delay tumor
growth and more important, to extend the lives of patients.
BENIGN AND MALIGNANT TUMORS CHARACTERISTICS
BENIGN TUMORS: CHARACTERISTICS
Benign tumors composed of well-differentiated cells that resemble the cells of the tissues of origin,
are characterized by a slow, progressive rate of growth that may come to a standstill or relapse.
Benign cells look like the tissues from which they arise. They grow by expansion and often remain
localized to their site of origin, lacking the capacity to infiltrate, invade or metastasize to distant sites.
They develop a surrounding rim of compressed connective tissue called a fibrous capsule which is
responsible for a sharp line of separation between the benign tumor and adjacent tissues known as
encapsulated which is a factor that facilitates surgical removal.
Benign tumors are less of a threat than malignant tumors. They usually don’t cause death to tissues,
blood vessels, or nerves unless they interfere with vital functions because of their location.
Benign tumors also can cause disturbances in the function of adjacent or distant structure by producing
pressure on tissues, blood vessels, or nerves.
They can also cause alterations in body function by abnormally producing hormones.
Named by adding suffix “oma” to the tissue type from which the growth originated.
Papilomas benign, microscopic or macroscopic finger-like projections that grow on any surface. MALIGNANT TUMORS: CHARACTERISTICS
Malignant neoplasms less well differentiated tumors that have lost the ability to control both cell
proliferation and differentiation into a mature cell.
Anaplasia loss of cell differentiation in cancerous tissue
Poorly differentiated poorly resembles the cell that it arose from. Undifferentiated malignant cells
are immature, embryonic in nature and no resemblance to the cell from which they arose.
Malignant cells grow rapidly and they grow in a disorganized and uncontrolled manner to invade
surrounding tissues and blood vessels. They rob normal tissue of essential nutrients and they release
enzymes, toxins and hormones called cytokines that destroy normal tissue.
They have cells that break loose and travel to distant sites to form metastases and inevitably cause
suffering and death unless their growth can be controlled through treatment.
Named by adding suffix “carcinoma” or “sarcoma” to the tissue type from which the growth originated
ETIOLOGY AND RISK FACTORS FOR CANCER
The etiology of cancer is multifactorial, with genetic, environmental, medical, and lifestyle factors
interacting to produce a given malignancy.
One can look at this process of carcinogenesis as a cause of cancer – that is how cancer is caused by
changes or mutations in a cell’s DNA or its genetic “blueprint”.
Heredity can pass on alterations in genes that make a person more susceptible to cancer.
Cancers come from random mutations that develop in body cells during one’s life, cancer is not
considered an inherited illness.
Inheritance of certain kinds of genetic alterations can influence a person’s chances of developing cancer.
All cancer is genetic (involving genes and DNA mutations) but small portion is inherited.
Sources of genetic information include DNA samples, and family history of disease. An accurate gene
test can tell if a mutation is present, but that finding does not guarantee that disease will develop.
Inherited mutations can influence a person’s risk of developing many types of cancer.
Concluding that an individual is at increased risk of developing cancer may have important, potentially
life-saving management implications and may lead to specific interventions aimed at reducing risk.
The chances of developing cancer increase as a person gets older because more time has been available
for mutations to accumulate. Therefore, age is a risk factor for developing cancer.
Cancer screening important as we age, involving checking for disease when there are no symptoms
Screening may find diseases at an early stage so there may be a better chance of curing the disease.
Canadian Cancer Society recommends that beginning at age 50, both men and women should be tested
for polyps with sigmoidoscopy or colonoscopy every 5 years.
The Ontario Breast Screening Program recommends that women aged 50 to 74 years with an average
risk for breast cancer receive a mammogram every two years, while women aged 30 to 69 years who are
identified as being at high risk for breast cancer should be screened annually.
Carcinogen (cancer causing agent) mutations which trigger changes in a cells genes that may be
caused by outside exposures. They are responsible for damaging DNA, promoting or aiding cancer.
Naturally occurring exposures (ex. radiation from sunlight) can cause cancer such as skin cancer.
Radiation exposure has been known to cause cancer. Exposure to certain chemicals such as benzene,
asbestos and smoke are also carcinogenic.
Certain viruses that infect human cells can also cause cancer. For example, transmission of the human
papillomavirus (HPV) during sexual relations can cause cervical cancer. Even medical treatments such as chemotherapy, radiation and immune system suppressing drugs may
make a person more susceptible to cancer.
Certain lifestyle risk factors that can be avoided increase the chance that a person will develop cancer.
People can help protect themselves by staying away from known risk factors whenever possible.
Having more than two alcoholic drinks each day for many years may increase the chance of developing
cancers of the mouth, throat, esophagus, larynx, liver, and breast. For most of these cancers, the risk is
higher for a drinker who uses tobacco which is one of the strongest cancer causing agents.
Obesity and physical inactivity may account for 25 to 30% of several major cancers.
People with a poor diet or whose diet is high in fat have an increased risk of cancer (ex. colon cancer).
The fluctuating levels of hormones in women such as during pregnancy, menstruation, etc. are linked to
risks of hormone-related cancers, such as breast and uterine cancer.
Evidence from both animal and human studies suggests that chronic stress and sleep deprivation
weakens a person’s immune system which in turn may affect the incidence of virus associated cancers.
NOMENCLATURE FOR NEOPLASMS
NOMENCLATURE: BENIGN TUMORS
Epithelial (Gland) Tissue
Thyroid Adenoma benign thyroid tumor, also known as a thyroid nodule. Patients may present with
hyperthyroidism symptoms (excessive sweating, nervousness, agitation, rapid heart rate, weight loss,
fatigue). Asymptomatic warm or cold adenomas and symptomatic is referred to as hot adenomas.
Pituitary Adenomas benign tumors arising from epithelial tissue in pituitary gland. They cause too
much prolactin secretory which can trigger breast milk production in non-lactating females and males
and amenorrhea (loss of menstrual periods) in females.
Fibroadenomas composed of fibrous and glandular tissue in the breast. Biopsy may be done to rule
out cancer. Fibroadenomas are easy to move with clearly defined edges.
Colon adenoma benign growth on surface of the colon (called polyp). Develop when there are errors
in the way cells grow and repair the lining of the colon. Some polyps have the potential to turn
cancerous. Removing them early prevents colorectal cancer.
Fibromas or skin tags increase in frequency as we age, more common in obese people. Most skin tags
are asymptomatic and benign. They can become irritated and inflamed. Recommended to remove skin
tags only when they are irritated or source of discomfort. Removed by tying or cutting them after
injecting a small amount of a local anaesthetic. They rarely become precancerous or cancerous.
Lipoma benign tumor composed of connective adipose tissue. They are soft to touch, usually
movable, and are generally painless. Many are small but can become bigger in size.
Osteoma new piece of bone growing on another piece of bone, it is a benign tumor. Larger
craniofacial osteomata may cause facial pain, headache, and infection due to obstructed nasofrontal
ducts. Craniofacial osteoma presents itself through ocular signs and symptoms.
Leiomyoma benign tissue of uterine muscle, commonly called uterine fibroids. They usually affect
women over age 30. The cause is unknown but fibroid growth seems to depend on the hormone
estrogen. Fibroid will continue to grow slowly as long as a woman with fibroids is menstruating. They
can be very tiny but can also grow very large. Common symptoms include abdominal fullness, gas or
constipation, bleeding between periods, increase in urinary frequency, heavy menstrual bleeding or
menorrhagia, menstrual periods that may last longer than normal, pelvic cramping or pain with periods
of sensation of fullness or pressure in the lower abdomen.
Rhabdomyoma benign tumor of striated muscle. Commonly associated with the tongue and heart. Neural Tissue
Neuroma benign tumor of nerve tissue, they can be applied to any swelling of a nerve.
Glioma benign tumor that starts in the brain or spine, arises from glial cells, brain is common site.
Meningioma benign tumor of the meninges. As they grow, they compress adjacent brain tissue.
Symptoms are related to the compression of brain tissue. Most are considered non-malignant or low
grade tumors. Some of these tumors can cause disability and may sometimes be life threatening.
Hemangioma benign tumor of the cells that line blood vessels, they are connected to the circulatory
system and filled with blood. Sometimes they grow in internal organs such as the liver. They may
present as a flat red or pink area. They are the most common childhood tumor, females are more likely
to have them. Many are located in face and neck, and the liver is the next prevalent location.
Lymphangiomas malformations of the lymphatic system (drains excess fluid from tissues). They can
occur at any age and may involve any part of the body. They cannot become malignant.
NOMENCLATURE: MALIGNANT TUMORS
These broad categories of tissue type help us to determine the types of cells affected.
Epithelial tissue, as you recall, is basically skin tissue that covers and lines the body. 2 categories of