Lec 1 Heme/Onc
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What are the 4 steps of carcinogenesis?
- 1. Initiation
- 2. Promotion
- 3. Conversion or transformation
- 4. Progression
Normal cells are exposed to carcinogenc substances, leading to genetic damage, leading to irreversible cellular mutations.
Carcinogens of other factors create an environment that favors growth of mutated cells over normal cells. This process is reversible.
Cell become cancerous. Could be years before diagnosis occurs.
Conversion or transformation
Tumor invasion into local and distal sites (metastasis).
What are the risk factors for development of cancer?
- 1. chemical: aniline dye exposure, benzene, smoking, drugs
- 2. physcial agents: radiation, UV lights
- 3. biologic: Epstein-Barr virus, HPV
- 4. age: > 50-60
- 5. gender: hormonal patterns
- 6. diet
- 7. chronic irritation: persistent cell damage & repair
- 8. family history: genetics
Which drugs are known to cause cancer?
- 1. alkylating agents
- 2. anabolic steroids
- 3. analgesics containing phenacetin
- 4. anthracyclines (doxorubicin)
- 5. antiestrogens (tamoxifen)
- 6. coal tar (topical)
- 7. estrogens
- 8. nonsteroidal (diethyl stilbestrol)
- 9. steroidal (estrogen replacement therapy, OC)
- 10. epipodophyllotoxins (etoposide, teniposide)
- 11. immunosuppressives (cyclosporine, azathioprine)
- 12. oxazaphosphorines (cyclophosphamide, ifosfamide)
What is an oncogene?
- develop from normal genes called protooncogenes
- protooncogenes --> oncogenes
What is a protooncogene?
- present in all cells
- regulate normal cell cycle & function
- alterations lead to oncogenes by means of point mutations, insertions, deletions & translocations
What are some examples of oncogenes?
What is the function of a tumor suppressor gene?
- regulate & inhibit inappropriate cell growth & cell proliferation
- mutation or loss of the gene leads to uncontrolled, unregulated, unchecked, unimpeded cell growth
- ex: p53, BRCA1, BRCA2, Rb1
What are the steps of the normal cell cycle?
- 1. cyclins and cyclin-dependent kinases (CDKs)
- 2. apoptosis
- 3. cellular senescence
What is the function of CDKs and how do they relate to cancer?
- Function: regulate checkpoints in the cell cycle
- dysfunctional or non-existent in cancer cells --> cells continue to proliferate unregulated
What is the function of apoptosis and how does it relate to cancer?
- Function: backup defense mechanism
- dysfunctional or non-existent in cancer cells --> increases risk for malignancy
What is the function of ellular senescence and how does it relate to cancer?
- Function: telomeres regulate the life-span of the cell (pre-set # of divisions); caps at the end of the chromosome
- protects DNA from damage
- shortened w/ each cell cycle
- telomerase is over-produced in cancer cells
If a tissue is identified as ending in -oma, what can be said about the state of that tissue?
If a tissue is identified as a carcinoma or a sarcoma, what can be said about the state of that tissue?
What are the mechanisms of tumorigenesis exhibited by most cancers?
- 1. self-sufficient in growth signals: activation of H-Ras oncogene
- 2. insensitive to anti-growth signals: loss of tumor suppressor genes
- 3. evades apoptosis: produces growth factor survival factors
- 4. limitless replicative potential: turns on telomerase
- 5. sustained angiogenesis: express vascular endothelial growth factor (VEGF) inducers
- 6. tissue invasion & metastasis: inactivation of E-cadherin
Identify the components of tumr staging, TNM.
- T = tumor (size & invasion)
- N = lymph node involvement
- M = metastasis (0= no; 1= yes)
Define the stages of cancer (1-4)
- Stage 1: localized cancer
- Stage 2-3: regional invasion (N > 1)
- Stage 4: metastatic cancer (M at least = 1)
What are the 4 modalities of treatment?
- 1. surgery (local)
- 2. radiation (local)
- 3. chemotherapy (systemic)
- 4. biologic therapy (systemic)
What is the treatment of choice for most solid tumors when possible?
Which modality of treatment destroys cancer cells in the early & some more advanced stages, helps eradicate cancer cells left behind by surgery and aids in tumor size reduction prior to other therapies?
Which modality of treatment is used for management & treatment of primary tumor & any metastatic disease?
What are the adverse effects of surgery for cancer treatment?
surgical complications, damage to surrounding tissue, possible metastasis
What are the adverse effects of radiation for cancer treatment?
irritation of the skin & tissue underneath, fatigue, infertility & secondary cancers are a possibility
What are the adverse effects of chemotherapy for cancer treatment?
N/V, alopecia, fatigue, myelosuppression (anemia, neutropenia, thrombocytopenia), mucositis, infertility, extravasation, cutaneous reactions, secondary malignancies
Which form of biologic therapy is broad? More specific?
- immunotherapy = broad
- targeted therapy = more specific
What is neoadjuvant therapy?
chemo administered before surgery or radiation (primary treatment)
What is adunctive therapy?
used concomitantly with primary treatment
What is adjuvant therapy?
given after the primary therapy to enhance possibility of a cure
What is palliative therapy?
to palliate or decrease symptoms of the cancer or its therapy
What is salvage therapy?
administered after primary therapy has failed (usually different regimen)
What is induction therapy?
1st step of therapy (loading dose or 1st chemo treatment)
What is consolidation therapy?
intensive chemo given after the inital induction therapy
What is maintenance therapy?
use of low dose chemo to promote lifelong remission
What year was Tamoxifen discovered?
What year did Tamoxifen prevential trials occur?
What year did proof of principle that chemoprevention works occur?
What year was BCG shown to prevent bladder cancer?
What year were antiestrogen drugs found to prevent DCIS?
What year was it discovered that Tamoxifen reduces breast cancer incidence?
What year was it discovered that finasteride reduces prostate cancer incidence?
What year was it found that aspirin prevents colon cancer?
What is the purpose of a performance scale (i.e., Karnofsky, ECOG)?
determines if a patient is healthy enough to tolerate chemotherapy
What does a patient's Karnofsky perfomance scale need to be for them to be eligible for chemotherapy?
- usually > 60%
- < 40% = significantly disabled and needs a lot of care & attention
What does a patient's ECOG score need to be in order to be considered elibile to receive chemotherapy?
- usually < 2
- 0= fully active
- 2= ambulatory & capable of self care but not able to carry out work activities
- 5= near death
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