HTHSCI 2PF3B - Cancer

cancer

cancer is the uncontrolled growth of abnormal cells in the body, cancerous cells are also called malignant cells, it is not a single disease (>200 types of cancer), oncology is the study of cancer, tumours & their treatment

cancer statistics

accounts for 15% of all deaths worldwide and 30% of all deaths in Canada, leading cause of death in Canada, 1 in 2 Canadians will develop cancer and 1 in 4 will die from it

cell cycle

• G0 phase - homeostasis, non-dividing stage

• G1 phase - growth phase

• S phase - DNA synthesis phase

• G2 phase - growth phase

• M phase - mitosis phase (cell division)

stem cells

produce progenitor cells when required, can differentiate into any type of cell

What cells continue to proliferate?

blood cells, skin cells, GI tract cells

What cells never or rarely proliferate?

nerve cells, muscle cells, cardiac cells

cell cycle checkpoints

• G1S checkpoint - checks for DNA damage, such as from radiation or chemicals

• G2M checkpoint - most important, checks for damaged or unduplicated DNA

carcinogenesis

• the process by which normal host cells are transformed into malignant cells resulting in the loss of normal growth control as cancer cells can divide infinitely

• cancer is a disease in which a single normal body cell undergoes a genetic transformation into a cancer cell, this cell and its descendants produce a population of cells known as a tumour

• slow progression allows for early detection

stages of carcinogenesis

initiation, promotion, progression

initiation

a normal cell acquires a genetic mutation due to carcinogenic agents, has the potential to develop into a cancer cell but is not yet fully malignant, cells are hyperplastic

promotion

unregulated and accelerated growth of mutated cells occurs, cells are dysplastic

progression

malignant tumour is formed, localized cancer is called in situ, invasive cancer can move into other areas of the body known as metastasis

types of DNA mutations

single base change, additions, or deletions, no DNA repair can lead to cancer

Proto-oncogenes

normal genes that regulate cell growth

oncogenes

mutated or damaged oncogene, promotes oncogenesis and accelerates cell growth and division

tumour suppressor genes

normal tumour suppressor genes prevent excessive growth and prevent cancer, removal, inactivation, or damage to both genes can lead to cancer, an inherited defect in one copy will not lead to cancer

p53 tumour suppressor protein

triggers cell suicide (apoptosis) in cells that have excessive DNA damage, most frequently mutated gene in human cancer

the immune system and cancer

natural killer (NK) cells and CD8+ T cells provide immune surveillance and destruction of cancer cells, our first and last defence against cancer

metastasis

the final stage in tumour progression is the migration and spread of cancers to different places from where they originated, the spread of cancer to other organs, most common sites for metastasis are the lymph nodes, lungs, liver, and bone as well as the peritoneum, adrenal gland, and skin or muscle

angiogenesis

metastasis requires angiogenesis which is the growth of a new network of blood vessels from existing vessels, allows small localized tumours to grow and spread, cancer cells make sure they can continue growing by stimulating the sprouting of new blood vessels to keep their nutrient supply lines open

normal cell angiogenesis

normal angiogenesis occurs in the developing fetus, the uterine lining, as well as in tissue during wound healing

tumour cell angiogenesis

cancer cells release signalling molecules that activate certain genes in host tissue that make proteins to encourage growth of new blood vessels

angiogenesis inhibitors

may be able to slow down or prevent growth and spread of cancer cells in humans, inhibitors are being tested as treatment, such as angiostatin, endostatin, interferons, platelet factor 4, thrombospondin, thalidomide, TIMP-1-3

characteristics of cancer cells

immortality, produce “go” signals, override “stop” signals, resist cell death or apoptosis (cell immortality), angiogenesis, metastasis

immortality of cancer cells

normal cells have a finite lifespan, cancer cells manipulate the cell to keep dividing indefinitely by producing proteins that enable them to do so

produce “go” signals

most cells wait for a “go” signal before dividing, cancer cells don’t bother waiting, they produce their own “go” chemical messages and continue dividing

override “stop” signals

even if neighbouring cells produce a “stop” signal, cancer cells override these signals and keep dividing

resist cell death or apoptosis (cell immortality)

normal cells sometimes react to age or mutations by triggering a “self-destruct” button and killing themselves, cancer cells sneak past these signals and continue to divide

risk factors for cancer

heredity, age, environment, lifestyle, cancer is multifactorial and a result of genetic, environmental, medical, and lifestyle factors interacting

heredity as a risk factor

• 5-10% of cancer is inherited

• identify at risk individuals through DNA testing and family history

• BRCA1 or BRCA2 mutations - 80% chance of breast cancer by 60

• potentially life-saving interventions can be used to reduce risk - tamoxifen (breast cancer), colonoscopy

age as a risk factor

• increasing age means more time has been available for mutations to occur

• screening can be done, high risk individuals should be screened earlier

  • prostate specific antigen (PSA) testing

  • fecal immunochemical test (FIT) - polyps (precancerous lesions) or colerectal cancer

  • colonoscopy

  • mammogram / MRI

  • clinical breast exam

  • pap smear - age 21

environment as a risk factor

• there are many different carcinogens

• UV light - sunlight, sunlamps, tanning beds

• radiation - CT scans

• chemical - benzene, asbestos, smoke

• bacteria - helicobacter pylori

• viruses - HPV (cervical), Hep B (liver), Epstein Barr (Burkitt’s lymphoma), HIV (Kaposis sarcoma), leukemias

• medical treatments - chemotherapy, radiation, immunosuppressive drugs

lifestyle as a risk factor

• alcohol ( > 2/day) - mouth, throat, esophagus, larynx, liver, breasts

• tobacco - lung, chronic lung & heart disease

• obesity - colon, breast, endometrial, kidney, esophagus

• diet

• hormone fluctuations - synthetic estrogen (DES) given to pregnant women can increase risk in daughters

• stress

• sleep deprivation

neoplasm or neoplastic

new growth

tumour

neoplastic growths

benign

noncancerous

malignant

cancerous

characteristics of benign tumours

• well differentiated - resemble normal cells

• slow growing - can stop or even regress

• look like tissues from which they arise

• localized - not invasive

• do not metastasize

• encapsulated

• can interfere with vital functions

benign tumour naming

add suffix “oma” to the tissue type, exceptions lymphoma, myeloma, melanoma

benign epithelial (gland) tissue tumour

“location” adenoma

benign adipose tissue tumour

lipoma

benign bone tissue tumour

osteoma

benign cartilage tissue tumour

chondroma

benign fibrous or connective tissue tumour

fibroma

benign smooth muscle tissue tumour

leiomyoma (ex. uterine fibroids)

benign skeletal or cardiac muscle tissue tumour

rhabdomyoma

benign neural tissue tumour

neuroma, glioma, meningioma

benign endothelial (lining of vessels) tissue tumour

hemangioma, lymphangioma

malignant tumour characteristics

• less well differentiated / anaplasia / poorly differentiated / undifferentiated - loss of cell differentiation in cancerous tissue

• do not resemble originating tissue

• rapid, disorganized growth patterns

• not encapsulated - invade local tissues, organs or blood vessels

• rob normal tissue of essential nutrients - release enzymes, toxins, hormones, cytokines that destroy normal tissue

• metastasize through blood and lymph

malignant tumour naming

• add suffix “carcinoma” or “sarcoma” to the tissue type

• carcinomas make up 85% of all cancers - epithelial tissue

• sarcomas make up less than 1% of cancers - bone, muscle, cartilage, connective tissue

malignant epithelial (gland) tissue tumour

adenocarcinoma “of location” (internal organs), squammous cell carcinoma “of location” (surface)

malignant fibrous tissue tumour

fibrosarcoma

malignant adipose tissue tumour

liposarcoma

malignant bone tissue tumour

osteosarcoma

malignant catilage tissue tumour

chondrosarcoma

malignant lymph tissue tumour

lymphosarcoma

malignant muscle tissue tumour

leiomyosarcoma, rabdomyosarcoma

malignant neural tissue tumour (brain tumours)

neuroblastoma, glioblastoma, meningeal sarcoma

malignant hematologic tumour

myelocytic leukemia, multiple myeloma, lymphocytic leukemia or lymphoma

malignant endothelial (lining of vessels) tissue tumour

hemangiosarcoma, lymphangiosarcoma

classifying malignant neoplasms

cell of origin, anaplasia or cell differentiation (Grade I to IV), anatomical location, stage of cancer, other prognostic factors

roman numeral staging

• stages I-IV establishes the amount of tumour in the body

  • stage I - small localized, curable

  • stage II - locally advanced

  • stage III - locally advanced, lymph node involvement

  • stage IV - inoperable, metastatic

• stage + letter

  • IA - no symptoms

  • IIB - symptoms such as fever, night sweats and weight loss

TNM classification

• Tumour (size of primary) - To - “in situ” → T4 - likely other organ invasion

• N: node involvement - No - no involvement → N4 - extensive involvement

• M: metastatic disease - Mo - no metastases → M1 - metastases

other staging tools

Clark’s levels for melanoma - depth not width, Gleeson score for prostate cancer - aggressiveness with higher numbers, Duke’s classification for colon cancer

other prognostic factors for staging

• rise in prostate specific antigen (PSA) in prostate cancer

• rise in carcinoembryonic antigen (CEA)

• rise in alpha-fetal protein (AFP)

• rise in cancer antigen 125 (CA125) - present on 80% of ovarian carcinomas

• ER+ (less aggressive hormonal treatment), ER- breast cancer

• tumour markers can help with diagnosis, treatment, and prognosis

drawbacks of staging

can’t always predict prognosis, only used as a guide, should look at pathology, operative and radiology reports, blood work, presenting symptoms and prognostic information

cancer treatments

surgery, radiation therapy, chemotherapy, hormonal therapy, biological therapy, stem cell transplantations, complimentary and alternative therapy (local and systemic therapy), adjuvant (combination) therapy

3 categories of cancer treatment

curative, control, palliative

reasons for surgery

• diagnosis - biopsy, tissue samples

• staging of cancer - biopsy

• tumour and/or surrounding tissue removal

  • cryosurgery - instillation of liquid nitrogen into tumour

  • chemosurgery - corrosive paste w/ surgical removal

  • laser surgery - small, precise surgeries

  • laparoscopic surgery - 2 incisions, 1 for viewing, 1 to perform surgery

• palliation when cure cannot be achieved

radiation therapy

• uses high-energy rays to destroy cancer cells, the absorption of energy from radiation in tissue leads to the ionization of molecules or creation of free radicals

• radiation can immediately kill cells, delay or halt cell cycle progression or produce damage to the cell’s DNA resulting in cell death after replication

• used as primary method, as adjuvant treatment, palliation, or oncological emergencies

• different types of radiotherapy include external, systemic, local, or internal

• can cause tiredness and alopecia

chemotherapy

• used as primary treatment as either single drug or combination chemotherapy (enhances effects & maximal cell kill), adjuvant treatment, or palliation

• normal healthy cells w/ rapid growth changes are most affected by chemo - blood cell forming bone marrow, hair follicles, lining of mouth & digestive system

chemotherapy classifications

• alkylating agents, antimetabolites, antitumour antibiotics, hormone and hormone antagonist, vinca plant alkaloids, miscellaneous anticancer drugs

• cell cycle phase specific drugs for actively growing tumours, minimal concentrations via continuous dosing

• cell cycle phase non-specific drugs for large non-growing tumours, single bolus injections

alkylating agents

cell cycle phase non specific (dividing or resting state), prevents nucleic acid duplication preventing mitosis in G2-M phase

antimetabolites

cell cycle phase specific (dividing state), block enzymes used in DNA synthesis or S phase

antitumour antibiotics

cell cycle phase non specific, disrupt DNA transcription and DNA and RNA synthesis

hormone and hormone antagonists

cell cycle phase non specific, prevent cell division and growth of hormone dependent tumours

vinca plant alkaloids

cell cycle phase specific, bind to proteins during metaphase causing mitotic arrest

miscellaneous anticancer drugs

cell cycle phase specific or non specific or both, inhibiting protein synthesis, blocking DNA replication or triggers cell death

hormonal therapy

tamoxifen to treat hormone receptor positive breast cancers - decreases estrogen and blocks its action

biotherapy

• uses body’s own immune system to fight cancers, triggers immune system to indirectly affect tumours

• cancer vaccines

• biological response modifiers

  • interferon

  • rituxan - non-Hodgkin’s lymphoma

  • herceptin - breast cancer

  • neupogen - controls side effects, increases WBCs & prevents infection in chemo patients

other cancer treatments

• targeted therapy (ex. thalidomide selectively attacks malignant cells)

• Bone marrow transplant and peripheral blood stem cell transplantation - replenish cells destroyed by treatment from yourself, twin, family, or unrelated donor

• complimentary and alternative therapy (CAM) - not considered standard care, acupuncture, special diets

integumentary system side effects of treatment

alopecia (temporary), hair thinning, local or systemic hypersensitivity reactions (allergies), extraversion (leakage of drugs to normal tissue requiring antidote), brusing and petechia (low platelets)

muscular system side effects of treatment

aches and pains, fatigue

nervous system side effects of treatment

neurotoxicity, ototoxicity (hearing changes), sleep disturbances, anxiety & depression, memory changes (“chemo fog”)

endocrine system side effects of treatment

• hypercalcemia

• hyperglycemia

• hyperkalemia - tumour lysis syndrome

• hypernatremia - dehydration, loss of body fluids, chemo causes vomiting

• hyperuricemia - tumour lysis syndrome

• dysfunction of endocrine glands - radiation

cardiovascular system side effects of treatment

cardiac toxicity - cyclophosphamide & doxorubican are drugs associated

digestive system side effects of treatment

hepatic toxicity, anorexia (loss of appetite), nausea & vomiting, constipation, diarrhea, mucositis / stomatitis

urinary system side effects of treatment

renal toxicity, cystitis (inflammation or bleeding of bladder lining requires administration of antidotes)

pulmonary system side effects of treatment

pulmonary toxicity, increased risk in patients over 70, monitor pulmonary changes

reproductive system side effects of treatment

reduced fertility, fetal death

lymphatic and hematological systems side effects of treatment

• neutropenia - low neutrophils

• thrombocytopenia - potential for life-threatening bleeding, may need platelet transfusion

• anemia - low Hct, hemoglobin, oxygen carrying capacity, may need packed red blood cells

• monitor CBC, WBC, and neutrophil counts, monitor for infection or sepsis, temperature, patient education is needed

How can you best assess for side effects in cancer patients?

for all body systems, assess baseline, then monitor for changes and treat side effects as needed