Cancer Flashcards
1
Q
What are the most common adult cancers?
A
Breast, lung, colorectal, prostate
2
Q
What are the most common peds cancers?
A
Leukemia, CNS, lymphoma, neuroblastoma
3
Q
What is the difference between a benign and malignant growth?
A
Benign: slow growth, well-defined, not invasive, well differentiated (resemble cells that they come from), low mitotic index (don’t divide quickly), does not metastasize.
Malignant: rapid growth, not encapsulated, invasive, poorly differentiated: anaplasia, high mitotic index, can spread distantly (metastasis)- usually via bloodstream
4
Q
Tell me about the biology of cancer cells.
A
- predominantly disease of aging
- clonal proliferation or expansion occurs
- mutations
5
Q
Tell me about mutations in oncology cells?
A
- alteration in DNA sequence affecting expression or function of a gene
- a cell that acquires characteristics that allow it to have selective advantage vs. other cells (ex. increased growth rate, decreased apoptosis)
- multiple mutations are required before cancer develops (due to a good fight from the immune system)
- immunosuppressed patients may be more at risk of Ca
6
Q
What are the different types of mutations amongst oncology cells?
A
Point mutations: small-scale changes
Driver mutations: “drive” progression of cancer
Passenger mutations: random events “along for the ride”
7
Q
What is gene amplification in oncology cells?
A
- repeated duplication of chromosome - proliferation
- 10s or 100s of gene copies made
- proliferation of cell development
8
Q
What is chromosome translocation?
A
- large changes in chromosome structure
- piece of 1 chromosome is translocated to another chromosome (ex. CML)
9
Q
What is clonal proliferation or clonal expansion?
A
- cancer cell progeny can accumulate faster than non-mutant neighbouring cells
- identical copy of cell before it
10
Q
What are the stages of human carcinogenesis?
A
- Activation of proto-oncogenes: results in hyperactivity of growth-related gene products (called oncogenes)
- Mutation of genes: results in the loss or inactivity of gene products that would normally inhibit growth (tumour-suppression genes)
- Further mutation of genes- proliferation: results in over-expression of products that prevent normal cell death or apoptosis, thus allowing continued growth of tumours.
11
Q
Explain the evasion of growth suppressors in cancer development.
A
- secretion of growth factors (via autocrine stimulation)
- increase in growth factor receptors
- mutation of the signal from cell surface receptor in the “on” position
- mutation in the Ras intracellular signalling protein
- inactivation of rentinoblastoma protein (Rb) tumour suppressor
- activation of protein kinases that drive the cell cycle
- mutation in the TP53 gene (tumour-suppressor gene)- suppression of normal apoptosis
12
Q
Explain the immortality of cancer cells.
A
- usually normal body cells are not immortal and can divide only a limited number of times (Hayflick limit)
- telomeres: protective caps on each chromosome that are held in place by a telomerase, become smaller and smaller with each division
- telomerase: an enzyme that protects the telomeres at the end of the chromosomes, inhibits apoptosis – immortal cell
- cancer cells can activate telomeres, leading to continued division- increasing production of telomerase
- cancer cells fail to inhibit telomere growth
13
Q
Tell me about angiogenesis in cancer.
A
- growth of new vessels = neovascularization
- advanced cancers can secrete angiogenic factors to facilitate feeding of tumour
- this is done by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)
- some forms of anti-VEGF therapy- which cuts off blood supply to tumour
14
Q
Tell me about cancer metabolism.
A
- cancer performs glycogenesis
- allows lactate and its metabolites to be used for the more efficient production of lipids and other molecular building blocks needed for rapid cell growth
- reverse Warburg effect: cancer cells generate large amount of ATP required for cell growth
15
Q
Tell me about inflammation in cancer.
A
- cause of cancer
- active inflammation predisposes a person to cancer by stimulating a wound-healing response that includes proliferation and new blood vessel growth
- susceptible organs: GI tract, pancreas, thyroid gland, prostate, urinary bladder, pleura, skin
- Example: ulcerative colitis for more than 10 years- 30-fold increase in developing colon cancer, Hep B/C- liver cancer risk, H.pylori- stomach cancer risk
16
Q
What is a tumour-associated macrophage (TAM)?
A
- key cell that promotes tumour survival
- develops capacity to block cytotoxic T cell and NK cell functions
- produces cytokines that are advantageous for tumour growth and spread
- secretes angiogenesis factors
17
Q
Tell me about immunotherapy (active & passive).
A
Active: immunization with tumour antigens to elicit or enhance the immune response against a particular cancer
Passive: injecting the patient diagnosed with cancer, antibodies or lymphocytes directed against the tumour-associated antigens
- less toxic than chemo
- does not effect rapidly growing cells
- adverse events associated
18
Q
What is metastasis?
A
- the spread of cancer cells from the site of original tumour to distant tissues and organs throughout the body
1. Spread (via lymph – circulation – organs)
2. Survive (attach to specific receptors)
3. Proliferate in distant locations, destination must be receptive to growth of cancer
19
Q
Tell me about the TNM system.
A
T- tumour (primary tumour size & extent)
N- nodes
M- metastases
20
Q
What are tumour markers?
A
- substances produced by benign or malignant cells
- found on or in a tumour cell, in the blood, spinal fluid, urine
- could be hormones, enzymes, genes, antigens, antibodies
- ex. PSA (prostate specific antigen)- marker to demonstrate whether tx was successful
- ex. CEA (carcinoembryonic antigen)- marker that may detect tumour of the bowel
21
Q
Explain the role of surgery in cancer.
A
- definitive tx for cancers that do not spread beyond the limits of surgical excision (ex.solid tumours)
- prevention of cancer (if you have at risk genes- BRCA 1/2)
- biopsy
- palliative: relief of symptoms (ex. urostomy tubes)
22
Q
Explain the role of radiation in cancer.
A
- used to kill cancer cells while minimizing damage to normal structures
- ionizing radiation – damages cells by importing enough ionizing radiation to cause molecular damage to the DNA, causes irreversible damage to normal cells, lifetime radiation dose, problem if relapse occurs
Bradytherapy:
- seeds are implanted
- internal radiation
- ex. prostate cancer tx
23
Q
Explain the role of chemotherapy in cancer.
A
- most common tx in disseminated cancers such as leukemia and lymphoma
- eradicates enough tumour cells to enable the body’s natural defences to eradicate the remaining cells
- single agent or combo chemo
- curative or palliative intent
- decreased therapeutic indices (less of the toxic drug needed with combo therapy)
Induction chemo: causes shrinkage or disappearance of tumours
Adjuvant chemo: administered after surgical excision with a goal of eliminating micrometases
Neoadjuvant chemo: administered before localized (surgery or radiation) treatment to “shrink” mass
8 major groups:
- Alkylating agents
- Platinum compounds
- Antimetabolites
- Hypomethylating agents
- Anti-tumour antibodies
- Mitotic inhibitors
- Topoisomerase inhibitors
- Miscellaneous
24
Q
What are the adverse effects of chemo?
A
common AE: N&V, hair loss, fatigue, diarrhea +/- constipation, neutropenia, bleeding (decreased plts)
- pneumonitis, colitis, hepatitis, nephritis = refer to oncologist, likely will treat with steroids
- T1DM, hypo/hyperthyroidism (monitor throughout tx, treat disorder), hypophysitis (inflam. of pituitary gland)- tx steroids
- febrile neutropenia
- may induce cancer (ex. leukemia after breast Ca tx)
25
What is febrile neutropenia?
- Decreased WBC and fever = sepsis
- oncologic emergency- timely tx <1 hr abx- call ER ahead of time
- Febrile neutropenia in those with solid tumours can often be treated with an outpatient regimen while those with hematological malignancy are often required to stay in hospital.
26
Tell me about anticancer drugs.
- work by targeting unique abilities of cancer cells (grow faster, metastasize)
- designed to "hit" cell replication through disruption of DNA synthesis at some point in the cell cycle- when a cell is replicating
- non-specific "buck shot" approach, kill cancer cells only slightly faster than normal cells, toxicities
- some drugs kill cancer cells only at certain phases of the cell cycle (phase specific)
- ex. works only when a high proportion of cells are dividing and only on cells that are in the right phase
- some drugs work throughout the cell cycle (phase non-specific)
- increase the immune system, hence AE: rash, diarrhea, hypothyroidism, hypophisitis (inflam. of pituitary gland)
- tx of AE: steroids, treat disorder, stop therapy
27
What is growth fraction?
- some cells are actively dividing and some are in the resting phase
- the ratio of proliferating cells to resting cells is called the growth factor
- most chemo drugs are more effective in conditions of high growth fraction
- the most common cancers (breast, lung, colon, prostate) have low growth fraction
28
List cancers that usually do respond to treatment, may respond and usually do not respond.
Do respond: Hodgkin's lymphoma, acute lymphoblastic (lymphocytic) leukemia, choriocarcinoma, wilm's tumour, testicular, other germ line cancers
May respond: breast, ovarian, endometrial, myeloma, large intestine, esophageal
Do not respond: thyroid, brain, liver, malignant melanoma, pancreatic, cervical
29
What are some modalities of supportive care with the treatment of cancer?
- abx therapy- prophylactic or responsive (ex. febrile neutropenia)
- antivirals/antifungals
- neupogen: help increase WBC's, to help prevent infection- AE: aches and pains of long bones (stimulation of bone marrow stem cell production) - may need pain management
30
What are the two types of polyps that can develop in the colon/ rectum?
- Adenomatous Polyps (adenoma): considered to be pre-cancerous. Cancer can form in a polyp, grow into the wall of the colon or rectum and then invade blood & lymph vessels; 95% of colorectal cancers are due to adenocarcinomas
- Hyperplastic polyps: due to inflammation & are not pre-cancerous
31
What is the relationship between DVT's and cancer?
- Patients with cancer are at four to sevenfold increased risk of venous thromboembolism (VTE) compared to those without cancer, making cancer associated thrombosis a major cause of mortality and morbidity
- dx: doppler, high rate of false positive d-dimer values in oncology patients
- tx: dalteparin, LMWH, rivaroxaban, apixaban (monitor for thrombocytopenia and active bleeding)
32
Tell me about biologic response modifiers.
Vaccines: immunotherapies to stimulate the immune system
Interferon-α: recombinant cytokine affecting tumor growth (direct antiproliferative effect, immunomodulatory effect on natural killer cells, T & B cells, and macrophages, induction of tumor cell antigens, a differentiating effect on tumor cells). Like the targeted therapies, interferon-α also has anti-angiogenesis effects.
Interleukin 2: recombinantly produced lymphokine that stimulates T and B cell proliferation and differentiation. Lymphoid cells that have been incubated with interleukin 2 were noted to have the ability to lyse tumour cells. Significant dose-related side effects were noted due to diffuse capillary leak that develops with therapy.
33
Tell me about the different screening associated with cervical, colorectal, breast, lung and prostate cancer.
See summary notes table
Colon- If average risk: FIT Q 2 years age 50-74. If FIT abnormal, colonoscopy should be done within 8 weeks.
If increased risk: first-degree fam member dx w/ colorectal cancer…
- If diagnosed @ < 60yr, colonoscopy Q 5 yr starting at 50 yrs or 10 yrs before age of dx
- If diagnosed @ > 60 yr, colonoscopy Q 10 yr starting at 50 yrs or 10 yrs before age of dx
Breast If no risk 50-74 years old, mammogram Q 2-3 years. Increased risk 30-60 years old, mammogram + breast MRI Q 1 year
- No clinical breast examinations or teaching about self-assessments
Lung Low-dose CT if age 55-74 with 20 cumulative years of daily smoking (new practice)
Cervical If sexually active or have been PAP Q 3 years age 21-70.
prostate NO screening
