Module 17 Flashcards
Uncontrolled proliferation of cells.
Cells of this type are often referred to as _________.
cancer
neoplastic
What are the 5 characteristics of cancer cells?
Persistent, uncontrollable cell proliferation Invasive Metastatic Immortal Angiogenesis
The ability of cancer cells to travel to different sites in the body and invade to form new tumours.
Metastatic
Cancer cells develop their own blood vessels to supply nutrients.
Angiogenesis
What are the three main treatment modalities for cancer?
Surgery
Radiation
Chemotherapy
Describe chemotherapy.
Drugs target rapidly dividing cells.
Describe radiation.
High energy radiation causes DNA damage to both cancerous, and non-cancerous cells.
Describe the stages of the cell cycle.
G1 - the cell prepares to duplicate its DNA S - synthesis of DNA G2 - the cell prepares for mitosis M - mitosis G0 - resting, cells do not replicate
Describe how toxicity to normal cells is an obstacle in chemotherapy.
Neoplastic cells are very similar to normal cells.
Cells with very high growth fractions are often affected by the toxic compounds.
What are some examples of cells with high growth fractions?
Bone marrow, GI epithelium, hair follicles, germinal epithelium of the testes (giving rise to sperm
Cure of cancer requires ____% cell kill.
100
Describe the kinetics of cell death with chemotherapy.
1st order
A constant percentage of cancerous cells are killed at a given dose
What are the three most prevalent cancers in Men in Ontario?
Women?
Men
- prostate, lung, colon and rectum
Women
- breast, lung, colon and rectum
Describe the screening protocols (Canadian) for breast cancer.
Clinical breast examination every 2 years starting at age 40, for women.
High risk patients are screened more often and screening may begin before age 40.
Describe the screening protocols (Canadian) for cervical cancer.
Sexually active women should have a Pap smear every 1-3 years.
Describe a Pap smear.
A speculum is insertred into the vagina, exposing the cervix.
A curette is then inserted into the endocervix.
Cells are scraped from the cervix and examined under a microscope to check for disease.
Describe the screening protocols (Canadian) for colorectal cancer/
Men and women (not high risk) should have a fecal occult blood test every two years.
Colonoscopy may also be eperformed evert 5 years in high risk patients
Describe the screening protocols (Canadian) for prostate cancer/
Men over 50 should have the Digital Rectal Exam and/or PSA blood test.
Describe the screening protocols (Canadian) for skin cancer.
(What do we look for?)
Self-checks should be performed regularly.
in particular, look for changes to birthmarks and/or moles, any new skin growths, and sores that don’t heal properly/
Describe the screening protocols (Canadian) for testicular cancer.
Males over the age of 15 should regularly perform the testicular self-examination
Why do ______ tumours respond poorly to chemotherapy?
Solid tumours
Respond poorly to chemotherapy as they have a large fraction of cells in the G0, resting, state. Thus, since chemotherapeutic agents target actively replicating cells, these are largely ineffective.
What are some ways in which cancer cells develop resistance to drugs?
Decreased drug uptake increased drug efflux Decreased drug acgivatoin Reduced target sensibitiy/increased cellular repair (mostly DNA) Decreased apoptosis
This pump can cause MDR.
P-gp
Describe intermittent chemotherapy.
The intent is to administer chemotherapeutic drugs intermittently, allowing normal cells to recover.
This only works if normal cells grow faster than cancerous cells
What are the reasons (3) that combination chemotherapy is more effective than administration of a single drug?
Decreased resistance
Increased cancer cell kill
Decreased injury to normal cells
Describe how using multiple drugs decreases drug resistance in cancer cells.
Resistance may be acquired from random mutations. These mutations are rare and the ability to develop resistance to many drugs simultaneously is very unlikely.
How can using more drugs cause decreased injury to normal cells?
Using drugs that do not have overlapping toxicities allows us to achieve greater anti-cancer effects more safely than we could with one drug alone.
The ____ ______ has a very high growth fraction and therefore is very susceptible to chemotherapy-associated toxicity.
Bone marrow
Bone marrow suppression may result in these.
Neutrophenia
Thrombocytopenia
Anemia
Describe digestive tract injury as a result of chemotherapy.
Stomatitis (inflammation of the oral mucosa) may develop. If severe enough, this may progress to ulceration.
Diarrhea may also occur secondary to damage to the intestinal epithelium.
Serious and common adverse effect associated with chemotherapy. Sometimes these effects are treatment limiting and patients will reufse further treatment because of the frequency.
Nausea and vomiting
What are some important adjuncts to therapy when nausea and vomiting are prevalent?
Anti-emetics, prevention of dehydration, prevention of malnutrtion
Anti-cancer drugs can be broken down into two major classes. What are they?
Cytotoxic agents
Hormonal and other agents
Only effective if the cancer cell is in a specific phase of the cell cycle.
What are they ineffective against?
Cell cycle phase specific drugs
Ineffective in cells that are in G0.
Can act during any stage of the cell cycle, including G0.
Cell cycle phase non-specific drugs
Describe the mechanism of action of Alkylating agents.
Highly reactive chemicals that act by transferring an alkyl group to cell components (mostly DNA).
They act by forming cross-bridges between nitrogen atoms on guanine nucleotides that make up our DNA.
Alkylating agents:
- effective in which phase?
- Most widely used drug in this class?
cell cycle phase non-specific - effective during any phase of the cell cycle
Cyclophosphamide - most widely used drug in the alkylating agents class
Describe cyclophosphamide (i.e. onset of action, activation).
Prodrug - converted to active from by the liver
Onset of action is thus delayed.
Describe the mechanism of action of platinum compounds.
Drugs with platinum in their chemical structure which act by cross-linking DNA. They bind to guanine molecules (similar to alkylating agents) and inhibit DNA replication.
Platinum compounds:
- Cell cycle phase specific/non-specific?
- Most widely used platinum compound?
Cell cycle phase non-specific
Cisplatin is the most widely used platinum compound
Cisplatin:
- Side effects?
Nephrotoxicity, ototoxicity, emetogenic (nausea and vomiting)
Describe the mechanism of action of antimetabolites.
Are structurally similar to natural compounds used by the body.
They act by inhibiting particular enzymes or preventing DNA replication.
Antimetabolites:
- Cell cycle phase ___________ ________
- What are the three subclasses?
Cell cycle phase specific –> mostly S phase
i) Folic Acid Analogs
ii) Purine Analogs
iii) Pyrimidine analogs
Describe the three classes of antimetabolites and their mechanisms of action.
Folic acid Analogs: Block the conversion of Folate to its active form.
Purine/Pyrimidine analogs: Inhibit the synthesis of DNA and RNA
Mechanism of action of anti-tumour antibiotics.
Kill cancer cells by intercalating DNA –> move between the bases of DNA and bind to DNA, causing a change in DNA structure, which makes the structure not able to be used as a template for DNA replication
Describe the administration of Anti-tumour antibiotics.
Poorly absorbed and thus given intravenously
Describe anthracyclines and their side effects.
Antitumour antibiotic, vert effective
Sides: bone marrow suppression, cardiotoxicity
