Cancer
January 6, 2018
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Cancer Definition: uncontrolled growth of abnormal cells in the body
o AKA malignant cells
o This mass of cells are composed of less well-differentiated cells that have lost the ability
to control both cell proliferation and differentiation in to mature cell
o Not a single disease -> >200 types of cancer
o Oncology: study of tumors and their treatment
 Looks at both benign and malignant tumors
Worldwide: 15% of all deaths
Canada: 30% of all deaths
o 2 in 5 Canadians will develop cancer
o 1 in 4 will die from cancer
Lung cancer is the leading cause of cancer death in both men and women -> accounts for over
50% of all cancer deaths each yr
Cell Cycle
o Cell Cycle: G Zero, G1, S (synthesis phase), G2 and M (Mitosis phase)
o IN a complete cell cycle a starting cell duplicates its contents and divides into 2 identical
daughter cells
o S phase: DNA is synthesized and chromosomes re replicated
o M phase: daughter cells are formed
o G Phases: major phase of cell cycle activity – cell is metabolically active or growing
enzymes or proteins in prep for DNA synthesis or mitotic divisions
o After mitosis, the daughter cells either go into a state of dormancy (G zero) were the cell
is not actively proliferating or if a stimulus for cell division exists, the cell enters the G1
phase to begin the cell reproductive cycle again
o Duration of M, G2 and S phase is relatively constant, whereas the time a cell spends in
G1 varies from a few hours to several days -> determines the overall length of the cell
cycle
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Cell cycle functions to allow for the process of cell proliferation
As the cell duplicates, there is an increase in cell number
As the cell divides and increases in number, the resulting daughter cells organize and become
differentiated/specialized
o Orderly process with increasing specialization occurring with each step
Three main categories of cells produced through cell differentiation and proliferation:
o Cells that never or rarely divide: nerve, skeletal or cardiac cells
o Progenitor cells: those that continue to proliferate and then die, particularly in areas
that have a high cell turnover such as the cells in the GI tract, skin and blood cells
o Stem cells: can enter the cell cycle and produce progenitor cell when required
 Remain quiet until needed, and then be called upon to produce daughter cells
of the type required
Stem cell transplant: method of replacing cancerous bone marrow with health stem cells
o Allogenic transplant: entail receiving donors stem cells
o Autologous transplant: entail receiving one’s own stem cells
o After diseased bone marrow is destroyed by chemotherapy and radiation, stem cells are
injected into the pt and these stem cells go on to proliferate into healthy blood cells
Cell Cycle: Checkpoints
o Cancer cells are able to complete the cell cycle more quickly by decreasing the length of
time spent in the G1 phase
 Much less likely to enter or remain in the G zero phase of the cell cycle than are
normal cells
o In most cells there are several checkpoints in the cell cycle at which tiem the cycle can
eb stopped if previous events have not been completed
o G1-S checkpoint monitors whether the DNA in the chromosomes is damaged by
radiation or chemicals
o G2-M checkpoint prevents entry into mitosis If DNA replication is not complete
o Transition from G2 to M is believed to be one of the most important checkpoints in the
cell cycle
o These checkpoints are actually a series of processes and proteins that help regulate cell
damage and repair
o These processes include a process of apoptosis, DNA repair system and Tumor
suppressor genes
Carcinogenesis
o Is the process by which normal cells are transformed into cancer cells
o Caused by a mutation of the genetic material of normal cells, which upsets the normal
balance between proliferation and cell death
o Results in uncontrolled cell division and tumor development in the body
o Normal cells undergo a finite number of divisions before they stop completely, cancer
cells have the capacity to undergo infinite number of cell divisions
o All cancer I genetic
o Cancer usually arises in a single cell
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Cell progress from normal to malignant to metastatic appears to involve a series
of distinct changes in the tumor and its immediate environment and each is
influenced by different sets of genes
Carcinogenesis: Stages
o Divided into three stages: initiation, promotion and progression
o Initiation:
 First step in the process of cancer development
 Involves the exposure of cells to appropriate doses of carcinogenic agent that
makes them susceptible to malignant transformation
 Carcinogenic agent can be chemical, physical or biological and produce
irreversible changes in the genome of previously normal cell
o Promotion
 Involves the unregulated and accelerated growth of the mutated cells
 Dysplasia is a term used in pathology t orefer to this abnormality of cell
development during the promotions stage
 Dysplasia is often indicative of an early neoplastic process
 i.e. pap smears can detect epithelial dysplasia of the cervix
o Progression
 Process whereby tumor cells acquire malignant changes and autonomous
growth tendencies that promote invasiveness and metastatic capabilities
Carcinoma in situ -> cancer in place
o Represents the transformation of a neoplastic lesion to one in which cells undergo
essentially no maturation, and thus may be considered cancer like
o Carcinoma in situ remains localized and has not invaded past the basement membrane
into tissues below the surface
o Invasive carcinoma is the final step in the sequence -> it is a cancer that has invaded
beyond the basement membrane and has potential to metastasize
One key feature of cervical cancer is its slow progression form normal cervical tissue to
dysplastic changes in the tissue to invasive to metastatic cancer
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Doesn’t always spread but when it does it spreads to lungs, liver, bladder, vagina and/or
rectum
Slow progression through numerous precancerous changes is very important bc it provides
opportunity for prevention and early detection and treatment
Genes control the cell cycle
Cell division is dependent on a tightly controlled sequence of events
o Which are dependent on the proper levels of transcription and translation of certain
genes
o If this process does not occur properly, unregulated cell growth may be the end result
Two genes have been identified in the initiation, promotion and progression of all different
kinds of cancer
o Proto-oncogenes: encourages cell division
 Mutation here: becomes oncogenes which stimulate excessive stimulation
o Tumor suppressor genes: inhibits cell division
 Mutation here: inactivates these genes, eliminating the critical inhibition of cell
division that normally prevents excessive growth => causes cancer
o Together, they coordinate the regulated growth that normally ensures that each tissue
and organ in the body maintains a size and structure that meets the body’s needs
Proto-oncogenes and oncogenes
o When oncogenes arise in normal cells, they can contribute to the development of
cancer by instructing cells to make proteins that stimulate excessive cell growth and
division
o Hyperactivity of the growth-signaling pathway
o A cancer cell may contain one or more oncogenes which means that one or more
components in this pathway will abnormal
o Most cancer causing mutation involving oncogenes are acquired, NOT INHERITED
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Tumor Suppressor Genes
o When DNA damage is detected, some tumor suppressor genes can send a “stop signal”
to the cell to stop it from multiplying until the damage is repaired
o Cells with DNA damage continue to divide, they can accumulate other DNA damage that
can eventually lead a cell to grow and divide in an uncontrolled fashion
o Individuals who inherit an increased risk of developing cancer often are born with one
defective copy of a tumor suppressor gene
 2nd copy of the gene from other parent, will still promote normal gene function
it’s only when the “good copy” gets damage may the person develop cancer
o Inherited abnormalities of tumor suppressor genes have been found in some family
cancer syndromes
 Causes a certain type of cancer to run in the family
o Defect in the APC gene causes familial adenomatous polyposis or FAP, a condition in
which ppl develop hundreds or even thousands of colon polyps -> often at least one,
becomes cancer
 Leads to colon cancer
Cells have at least 3 other systems that can help them avoid runaway cell division
DNA Repair System
o Instruct a cell to repair damaged DNA
o System operates in virtually every cell in the body
o Detect and correct errors in DNA
o Across a lifetime, the DNA is constantly under attack from external or internal
carcinogens
o Simplest type of mutation involves a change in a single base sequence of a particular
gene -> like a typographical error
 One or more bases may be added or deleted
 Sometimes large segments of DNA are accidentally repeated, deleted or moved
o Error also occurs during DNA replication
 In most cases, these error are rapidly corrected by the cell’s DNA repair system
BUT mutations in this DNA repair system can lead to a failure in repair which in
turn allows subsequent mutation to become a permanent feature in that cell
and in all of its descendants
o Pts with Xeroderma pigmentosum have an inherited defect in a DNA repair system
 They cannot effectively repair the DNA damage that normally occurs when skin
cells are exposed to sunlight and so they exhibit an abnormally high incidence of
skin cancer
Mismatch Repair
o DNA polymerase copies both strands of the DNA – top and bottom
 AKA Watson and Crick strands
o Sometimes the polymerase makes mistakes -> i.e. may incorporate the wrong
nucleotide
o Repair proteins MSH2, MSH6, MLH1 and PMS2 recruit another enzyme called EXO1
(exonuclease) which chops off the mutant strand
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It then allows a DNA polymerase to come by and synthesize the correct strand, therby
fixing the DNA and making it normal
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Apoptosis
o Old cells become damaged over time and are eliminated by apoptosis
o Stimulate cells with damaged DNA to “commit cell suicide”
o Tumor suppressor p53 protein, initiates cell suicide
o Mutation in p53 gene has been found in 50% of human cancers including lung,
colorectal and breast cancer
o Most frequent mutated gene associated w cancer
NK cell and the immune system
o First and last defense against cancer
o NK cells are a part of the immune system and are very important bc they can
target tumors and cancer cell and kill them
o A number of chemo drugs need the immune system to be intact for the drugs to
be effective
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Metastasis: spread of cancer from its original location to other parts of the body
o Critical event in cancer
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About 90% of the death associated with cancer is due to the spread
Can occur in two ways
 Mlignant cells can directly invade or extend into adjacent organs or sites
 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 distant capillary beds where they
can grow until they burst through a cap wall
Angiogenesis
o Process of forming new blood vessels
o One of the critical events required for cancer metastasis
o Begins when a tumor becomes large enough where it needs to increase the supply of
nutrient and O2 it receives
o Low O2 or hypoxia trigger the tumor and its surrounding environ to release signals that
result in the growth of blood vessels towards and into the tumor
o This allows the tumor to continue growing
o Occurs normally in the human body at specific times in development and growth
o I.e. child developing in womb, in uterine lining during the menstrual cycle, repair or
regeneration of tissue during wound healing
Tumor Cell Angiogenesis
o Proliferation of a network of blood vessels that penetrates into cancerous growth,
supplying nutrient and O2 and removing waste products
o Starts with tumor cells releasing molecules that send signals to surrounding normal host
tissue which activates certain genes in host tissue which makes protein to encourage
growth of new blood vessels
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Angiogenesis inhibitors
o Over two dozen angiogenesis inhibitors are currently being tested in cancer pts
o One class being tested are molecules that directly inhibit the growth of endothelial cells
 endostatin the naturally occurring protein know to inhibit tumor growth in
animals
o Thalidomide
 Drug used in the 50s as a sedative but was taken off the market bc it caused
birth defects in women
 BUT it does prevent endothelial cells from forming new blood vessels which can
be useful in treating cancer pts
o Second group are currently being tested on humans which are molecules that interfere
with steps in angiogenesis signaling cascade
 i.e. Avastin -> proven to delay tumor growth and extend pt lives
o Interferon-alpha
 Naturally occurring protein that inhibits the production of growth factors form
starting the angiogenesis signaling cascade
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Etiology of cancer is multifactorial with genetic, enviro, medical and lifestyle factors interacting
to produce a given malignancy
5-10% of cancer is inherited
o However, a person’s chance of developing cancer can be influenced by the inheritance
of certain kinds of genetic alterations
Identify at risk individuals
Women with the BRCA1 or BRCA2 mutations have an 80% chance of developing breast cancer
by the age of 65
o About 5% of breast cancer is thought to be inherited
Potentially life-saving interventions aimed at reducing risk
Age as a risk factor
o Since ppl are living longer they are exposed to more carcinogens
o Prostate cancer is rarely seen in men younger than 40yrs –> incidence rises rapidly with
each decade
o Screening:
 Prostate Specific Agent (PSA) Testing
 Digital rectal exam -> assessment of prostate with gloved finger via rectum
 Fecal occult blood
 Colonoscopy
 Mammogram -> Every 2yrs for women 50-69 unless they are high risk for breast
cancer in which case women 30-69 are screened q1yr
 Clinical breast exam
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Environment as a risk factor
o Carcinogens
 UV light
 Radiation
 Chemical -> benzenes, asbestos and smoke
 Bacterial
 Viruses -> HPV, Epstein Barr Virus increases risk of developing Burkitts
Lymphoma, Hep B may increase chance of Liver cancer, HIV increases chance of
developing Kaposi’s sarcoma (sarcoma -> tumor/cancer affecting connective
tissue)
 Medical treatments
Lifestyle as a risk
o Alcohol -> having more than 2 alcoholic drinks per day for many yrs increases the
chance of developing cancers of mouth, throat, esophagus, larynx, liver and breast
o Tobacco -> strongest cancer causing agents
 Associated with lung cancer, chronic lung disease and CVD
o Obesity and physical inactivity
 May account for 25-30% of several major cancers including colon, breast,
endometrial, kidney and esophageal
 Failure to limit adult weight gain may account for 1/3 of all breast cancers
 Some studies have also reported links bw obesity and gallbladder, ovarian and
pancreatic cancers
o Diet -> diets high in fat have an increased risk for cancers of the colon, uterus and
prostate
o Hormones
 Menopausal hormone therapy may increase risk of breast cancer, heart attack,
stroke or blood clots
 Diethylstilbestrol or DES increase risk of breast cancer in pregnant women and
increase risk of developing a rare cervical cancer in those mother’s daughters
(given from 1940s-1970s)
 Fluctuation of hormones during a menstrual cycle may increase risk of
hormone-related cancers such as breast and uterine cancer
o Stress
o Sleep deprivation
 Decreases immunity which may increase risk of virus/bacteria associated
cancers
Nomenclature
o Neoplasic growths and tumors are used interchangeably
o Neoplastic -> benign or malignant
 Useful way of classifying and naming tumors based on site of origin
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Benign Tumor: Characteristics
o Well differentiated
o Slow growing -> may come to standstill or even regress
o Look like tissue from which they arise
 For unknown reasons, benign tumors have lost ability to suppress the genetic
program for cell proliferation but have retained program for normal cell
differentiation
o Localized -> not invasive and grow by expansion
o Do not metastasize
o Encapsulated
 Bc they expand slowly
 Develop surrounding rim of compressed connective tissue called a fibrous
capsule
 Capsule is responsible for sharp line of demarcation between the benign tumor
and adjacent tissue -> FACILITATES SURGIVAL REMOVAL
o Can interfere w vital functions but do not cause death of tissue unless they interfere
with vital functions due to location
o Add suffix “oma” to the tissue type
Lipoma
o Benign tumor composed of connective adipose tissue -> soft to touch, usually movable
and are generally painless
o Usually under 1cm
Glioma
o Type of benign tumor that starts in brain or spine
o Arises from glial cells
Malignant Tumors: Characteristics
o Less well differentiated/Anaplasia
 Anaplasia: describes loss of cell differentiation in cancerous tissue
 Poorly differentiated
 Undifferentiated -> immature, embryonic in nature and there is no resemblance
to the cell from which they arose
o Do not resemble originating tissue
o Rapid, disorganized growth patterns
o Not encapsulated: invade local tissue, organs and blood vessels
o Rob normal tissues of essential nutrients
o Release cytokines that destroy norm tissue
o Metastasize through blood and lymph
o Add suffix “carcinoma” or “sarcoma” to the tissue type
Cancers that are derived from cells of glandular origins or epithelial tissue type are known as
carcinomas
Connective tissue cancers are called sarcomas
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Classifying Malignant Neoplasms
o No simple and single method of classifying malignant neoplasm
o Classified using a variety of classification schemes and/or combination of classifications
 Cell of Origin -> alone, is not specific enough
 Anaplasia or cell differentiation -> the closer the tumor cell resembles
comparable norm tissue, both morphologically and functionally, the lower the
grade
 Tumor Grade ->measure of how abnormal cells from the tumor appear
under the microscope which can refer to appearance of cells or
percentage that appear to be dividing
o Grade I: well differentiated cells
o Grade IV: poorly differentiated and display marked Anaplasia
 Anatomical location from which the tumor arises
 “The primary tumor” -> initial tumor
 Stage of the cancer -> describes how far cancer has spread anatomically
 Attempt to put pts w similar prognosis and treatment in the same
staging group
 Prognosis and treatment depend on staging so it’s very important
 For solid tumors there are two related staging systems: Overall Stage
Grouping and TNM system
 Other prognostic factors
Staging Malignant Tumors w Roman Numerals
o Stage I: small localized, curable
o Stage II: locally advanced
o Stage III: locally advanced, lymph node involvement
o Stage IV: inoperable, metastatic
o Stage + Letter:
 A: no symptoms
 B: symptoms such as fever, night sweats and weight loss
 Allows for small differences which are very significant -> i.e. IIIa have a chance
of being cured w treatment
o Important to realize that the prognosis for a given stage depends on what kind of cancer
it is
o Not the whole story -> many individual situations etc.
 Sometimes treatment depends on where the metastases are located etc.
o General guide, many variations on outcome despite staging
TNM Classification
o Tumor: size of primary
 Rating of 0-4
 0: tumor that has not even started to invade the local tissues (in situ)
 4: large primary tumor that has probably invaded other organs by direct
extensions and which is usually inoperable
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Node involvement
 Involvement of distant nodes is considered metastatic disease
 Score of 0-4
 0: no involvement
 4: extensive involvement -> some combination of more nodes involved, greater
enlargement of the involved nodes and more distant (but still regional) node
involvement
Metastatic disease
 M: no metastases
 M1: there are metastases
This system is more precise vs I-IV staging
Does not apply to cancers that do not form solid tumors like leukemias -> use the
staging model
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Prognostic Factors
o Molecular tests play a significant role in contributing to staging of the disease
o Prostate Specific Antigen (PSA)
 Substance mostly made in prostate
 May be found in increased amounts in men who have prostate cancer
 Can be a marker for prostate cancer BUT is not a perfect tool -> levels may be
high in those who have an inflamed prostate or have a benign tumor
 Need PSA testing + digital rectal exam
o Carcinoembryonic antigen (CEA)
 Can be found on many different cells but is usually associated w both malignant
and benign tumors
 Colon cancer most frequently causes increased CEA levels
 Best marker of GI cancers
 Other cancers that causes increased CEA: pancreatic, stomach, breast, lung and
some type of thyroid cancers
 Smoking, infection, IBS, pancreatitis, cirrhosis of liver
 Rising of CEW levels indicates progression or recurrence of cancer
o Alpha-fetal protein (AFP)
 Synthesized by liver, yolk sac and GI
 Normally detected in pregnant women
 Rarely elevated in a few disease states such as liver disease (hepatitis, cirrhosis)
and hepatocellular carcinoma (liver cancer)
 Less frequently elevated in other malignancies such as pancreatic cancers,
gastric, colonic cancer and bronchogenic cancers
 Elevation was not necessarily associated w liver metastases
o Cancer Antigen 125 (CA125)
 Present in 80% of ovarian carcinomas
 Decreasing rates shows that treatment is effective
o Estrogen receptor + and estrogen receptor – (ER+, ER-)
 Determines treatment option of breast cancer
 ER+ have receptors for estrogen on their surface
 Often require the presence of estrogen for growth
 More affected by hormonal treatment and tend to be less aggressive
Cancer treatment
o Goal of treatment
 Curative
 Control
 Palliative
o Depends mainly on type of cancer and stage of disease
o Docs also consider pt’s age and general health
o Types of treatment
 Surgery
 Radiation Therapy
 Chemotherapy
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Hormonal Therapy
Biological Therapy
Stem cell transplantation -> may be done so that a pt can receive a very high
dose of chemo or radiation
 Complementary and Alternative Therapy -> increased use of these
 Local -> removes or destroys cancer in just one part of the body (i.e.
surgery, radiation)
 Systemic -> sends drugs or substances through the bloodstream to
destroy cancer cells all over the body (i.e. chemo, hormone therapy and
biological therapy)
o Adjuvant therapy -> giving therapy in combination with another
Reason for having surgery:
o To diagnose cancer
 Surgeon tries to remove the tumor and some tissue around it
 Done for biopsy and to stage
o To determine the stage of cancer
o To remove the rumor and/or surrounding tissue
 Removing nearby tissue may help prevent the tumor from growing back
 May also remove nearby lymph nodes
 Cryosurgery -> involves the instillation of liquid nitrogen into the tumor through
a probe
 Used to treat some liver and prostate cancer
 Chemosurgery -> use of corrosive paste in combo with surgically removing
multiple frozen section of the tumor (mainly used for skin cancers)
 Laser surgery -> involves the surgeon using laser beam to resect a tumor
 Effective for very small, precise surgeries such as the retina or vocal
cords
 Laparoscopic surgery -> surgeon making two small incisions in the surgical area,
one for viewing and the other for inserting the instrument to perform the
surgery
o To palliate and help relieve symptoms when cure is no longer available
Radiation Therapy
o Use of high energy rays to destroy cancer cells
 Absorption of energy from radiation in tissue leads to the ionization of molecule
or creation of ROS
o Radiation can immediately kills cells, delay or halt cell cycle progression or produce
damage to the cell’s DNA resulting in cell death after replication
o Can be used as a the primary method or part of adjuvant treatment
o Palliative -> to reduce symptoms such as bone pain resulting from metastases
o Oncological emergencies -> i.e. reducing tumor size that would be causing spinal cord
compression or bronchial obstruction
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Types of Radiotherapy
o External
 When radiation comes from a large machine outside the body
 External radiation can be given systemically or locally (beam of radiation is
directed right at the tumor location)
o Systemic
o Local
o Internal i.e. brachytherapy is used as an effective treatment for cervical or prostate
cancers
Since most of radiation therapy is local therapy, many side effects are related to the specific
area being treated
Side effects depend mainly of the dose and type of radiation
Alopecia -> hair loss
Many who experience radiation treatment become very tired especially in he later weeks of
treatment
Chemotherapy
o AKA antineoplastic agents
o Major systemic treatment modality for cancer
o Primary or adjuvant treatment
 Single drug treatment
 Combo chemo -> enhances the effect of the drugs on the tumor cell
 Maximal cell kill within the range of toxicity tolerated by a pt
 Broader range of coverage
o Palliative
o Slow or stop cancer cells from growing, multiplying or spreading to other parts of the
body
o Tumor cells more sensitive than normal cells to chemo agents that are toxic to rapidly
dividing cells
 Damages healthy cells that grow and change rapidly i.e. hair follicles, lining of
the mouth, GI, bone marrow
o Should be given in session to allow for rest periods
Mechanism of most chemo drugs is to target the DNA some how
o May result in interference with the DNA, inhibition of enzymes related to RNA or DNA
synthesis or both and/or destruction of the cells necessary proteins
Chemo drugs are given according to schedules that have proved most effective for tumor kill
and that are planned to allow normal cells to recover
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Cell cycle specific chemo drugs
o Active on cells undergoing division in the cell cycle
o Most effective against actively growing tumors that have a greater proportion of cells
cycling through the phase in which the drug attacks the cancer cell
o Given in minimal concentration via continuous dosing methods
Cell cycle non-specific chemo drugs
o Active on ells in either a dividing or resting state
o Active in all phases of the cell cycle and may be effective in large tumors that have few
active cells dividing at the time of admin
o Often given as single, bolus injections
Hormone Therapy
o Admin of drugs that disrupt the hormonal environment of cancer cells
o Used for cancers that are responsive to or depending on hormones for growth
o 80% of breast cancers are ER+ meaning it can be treated by (done via hormone therapy)
 Lowering the amount of estrogen in the body
 By blocking the action of strong on the breast cancer cells
o Can help shrink or slow the growth of advanced-stage or metastatic hormone receptor
positive breast cancers
o NOT effective vs ER- breast cancers
o Examples of therapies: aromatase inhibitors, selective estrogen receptor modulators
and estrogen receptor own regulators
o NOT the same as hormone replacement therapy
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Biotherapy
o Uses the body’s own immune system to fight cancer and to reduce treatment related
side effects
o Often provided in conjunction
o Cancer vaccines
 Currently developing vaccines that may encourage the pt’s immune system to
recognize cancer cells
 Would work in similar ways as measles or mumps vaccines
 BUT are used after someone has cancer -> Vaccine would be given to prevent
the cancer from returning or to get the body to reject the tumor lumps
o Biological Response Modifiers
 Able to trigger the immune system to indirectly affect tumors
 Involves giving larger amounts of these substances by injection or infusion in the
hope of stimulating immune cells to act more effectively
 I.e. interferon alpha, Rituxan or Rituximab which treats non-Hodgkin’s
lymphoma and Herceptin which treats breast cancer
 Used in controlling side effect of treatment including Neupogen or G-CSF which
increases WBC accounts and help prevent infection in ppl who are getting
chemo
Target Therapy
o AKA molecular targeted drugs
o Substance that selectively attack malignant cells while leaving normal cells unharmed
o In clinical studies
o Interfere with cancer cell division, processes of apoptosis or angiogenesis
 Therefore, requires food identification of targets
o I.e. Thalidomide
BMT and PBSCT
o Bone marrow transplantation (BMT)
o Peripheral blood stem cell transplantation (PBSCT)
o Both are procedures that restore stem cells that have been destroyed by high doses of
chemo and/or radiation
o Three types of transplant
 Autologous -> their own stem cells
 Syngeneic -> receives stem cells from identical twin
 Allogeneic -> receives stem cell from brother, sister, parents etc. (non-related
donor may be used as well)
o After harsh chemo, the damaged bone marrow is unable to produce blood cells needed
to carry O2, fight infection and prevent bleeding
o Transplantation replaces the bad for the good marrow
Complementary and Alternative Therapy (CAM)
o Used along w standard medical treatments
o i.e. use of acupuncture or diet
Integumentary Symptoms
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Alopecia
o Hair loss occurs 10-21 days after drug treatment
o Temporary and will regrow when drug is discontinued
Hair thinning -> Pts should be instructed to keep the head covered to prevent sunburn and heat
loss
Local or systemic hypersensitivity reactions
o Review pt’s allergy hx
o Monitor for hypersensitivity or anaphylaxis
o Test doses as ordered
o Maintain good personal hygiene
o Avoid perfumed lotions
Extravasation
o Inadvertent leakage of chemo drug form a vessel into surrounding tissue
o Assess for immediate or delayed pain, tightness, blister or sloughing of tissues
o Management includes prompt admin of antidotes to minimize tissue damage
Petechia
o Pinpoint hemorrhages on skin and mucous membs caused by low platelet count
o Chemo and radiation therapy can cause low platelet counts which might manifest itself
in pt having petechial
o Thrombocytopenia or low platelet count should be monitored
o Pt should be instructed to avoid use of razors and invasive procedures
Muscular Symptoms
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Aches and pains -> pain meds may alleviate aches and pains associated w treatment
Fatigue -> pts should be encouraged to conserve energy and plan rest periods
Neuronal Symptoms
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Neurotoxicity
o Certain chemo agents such as vinblastine, vincristine and etoposide can cause
neurotoxicity
o Monitor for sympts of weakness, numbness, tingling extremities and foot drop
Ototoxicity
o Certain chemo agents can cause hearing changes
o Baseline audiograms and monitor for symptoms of tinnitus, hearing loss and vertigo
Sleep patter disturbances
o Cancer pts are at greater risk for developing insomnia and disorders of the sleep-wake
cycle
o Insomnia is the most common sleep disturbance in this pop
o Most often secondary to physical and/or physiological factors related to cancer and/or
cancer treatment
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Meds including vits, corticosteroids and neuroleptics for nausea and vomiting well as
other treatment factors can –vely impact sleep patterns
Anxiety and depression
o Are common psychological response to the dx of cancer, cancer treatment and
hospitalization
o Pts should be encouraged to set small achievable daily goals, participate in enjoyable
and divisional activities and share their feelings and concerns w someone
Memory changes
o Can result as a side effect of chemo
o Many pts refer to this as “chemo fog”
o Helpful management tops for pts include:
 Using calendars and lists to write down info and tasks
 Providing pill boxes or docettes to help admin meds
Endocrine Symptoms
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Hypercalcemia
o As chemo destroys cancer cells, some cancer cells secrete substances that cause calcium
to be absorbed into bloodstream from bone
o Monitor calcium levels, polyuria and mental status change
Hyperglycemia -> many pts are on steroids for this disease and develop high blood sugar levels
Hyperkalemia (As seen w tumor lysis syndrome)
o When pts receive chemo, the drugs will act by breaking down the tumor cells
o When there is a rapid amount of cellular destruction, the components of the cells
(including destruction) will move outside of the cell and into the blood stream
o Pts who receive chemo for leukemia lymphoma or multiple myeloma may be at risk of
tumor lysys syndrome if there is a large amount of disease present
Hypernatremia
o May be caused by dehydration or a loss of body fluids from prolonged vomiting,
diarrhea, sweating or high fever
o Monitor serum sodium levels
o Observe symptoms of thirst, dry mucous membs, poor skin turgor, restlessness and
lethargy
Hyperuricemia
o After chemo, there is often a rapid amount of cellular destruction and tumor lysis
syndrome may occur
o Monitor serum and urine uric acid levels
o Daily ins and outs, rigorous hydration if indicated
Cardiovascular Symptoms
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Cardiac toxicity
o Drugs associated w potential cardiac toxicity include cyclophosphamide and doxorubicin
o Baseline cardiac studies (ECG, echo, cardiac enzymes) before chemo admin
o Monitor cardiac status and cumulative doses of chemo agents
Digestive System Symptoms
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Hepatotoxicity
o Some chemo drugs are associated w potential liver toxicity
o Monitor liver functions tests
o Assess for jaundice
o Tenderness over the liver
o Urine and stool color changes
Anorexia
o Many pt undergo radiation and/or chemo report loss of appetite
o Encourage pts to eat small frequent meals, eating foods high in protein
o Monitor weight
Nausea and vomiting
o Many pts undergo radiation and/or chemo experience it
o Some chemo drugs have high emetic potential -> cisplatin, daunorubicin, high dose
cytarabine, cyclophosphamide and methotrexate
o Management includes eating small, frequent meals
o Avoid fatty and salty foods
o Encourage liquids
o Admin of antiemetic meds
Constipation
o Side effect of radiation of certain chemo drugs
o Can also be a symptom of dehydration
o Management includes high fiber diet, stool softeners and increased fluids
Diarrhea
o Can be a side effect of radiation of certain chemo drugs
o Management: avoid greasy and spicy foods, eating a bland diet, monitor bowel
movements, monitor fluid intake and electrolytes
Mucositis/stomatitis
o Symptoms appear 3-5 days after local radiation treatment or systemic chemo agents
o May be painful enough to require analgesic IV drip
o Management includes eating small bland frequent meals, using a non-irritating mouth
wash
o Assessing for oral thrush
Urinary Symptoms
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Renal Toxicity
o Certain chemo agents can cause renal toxicity
o Management: assessing baseline renal function, encouraging oral intake, moniro I&O
and weight changes
Cystitis
o Some chemo agents can cause inflame and even bleeding of the bladder lining
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Management includes increasing fluid intake, emptying bladder frequently and admin
antidote drugs such as MESNA
Pulmonary Symptoms
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Pulmonary toxicity
o Local radiation treatment and certain chemo agents can cause pulmonary changes
o Individual over 70 at greatest risk
o Management includes assessment of baseline resp function, ongoing assessment of resp
status
Reproductive Symptoms
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Reduced fertility
o Cancer pts should be informed of options for fertility preservation and future
reproduction prior to cancer therapy
Fetal death
o Cancer treatment will result in reduced fertility and fetal death
Lymphatic and Hematological Symptoms
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Neutropenia -> less than 2000 cells per cubic mm
Thrombocytopenia -> reduction in the number of circulating platelets below 30,000 cubic mm
Anemia -> abnormal or low hematocrit and/or haemoglobin levels below 80g/L