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35 Cards in this Set
- Front
- Back
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What is the multi-step model of carcinogenesis?
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Normal --> dysplasia --> in situ cancer --> invasive cancer --> metastasis.
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What four things do all cancers show?
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1. Inappropriate proliferation,
2. resistance to differentiation and apoptosis, 3. Genomic instability, and 4. Ability to grow where it ought now (malignant growth.) |
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What is senescence?
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Permanent growth arrest induced by anti-proliferative signals from tumor suppressor genes like p16 and p53.
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The lesioning of what pathway leads to transformation to cancer cells?
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p16-cyclinD-cdk4-Rb pathway
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Why would a cancer cell want to reactivate telomerase?
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A cancer cell would want to use telomerase to lengthen its telomeres to avoid the process of senescence.
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What genetic event is associated with differentiation blocks in many acute myeloid leukemias?
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Inactivation of core binding factor (CBF) activity.
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The disruption of what pathway creates a differentiation block that is associated with many solid tumors?
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WNT-APC-b-catenin pathway (ex: breast and colon cancer)
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What is a "cancer stem cell"?
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A self-renewing tumor cell that is more resistant to treatment than its progeny because it divides less frequently.
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What induces apoptosis?
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Hypoxia, DNA damage (chemotherapy), oncogene activation, telomere shortening.
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What pathway contributes to both senescence and apoptosis?
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p53
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Why is genomic instability bad for cancer therapy?
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Ex: Gleevec (Imatinib) inhibits ABL, keeps CML in check. Progression of cancer related to imatinib-R ABL mutations.
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What is the function of the BRCA1 gene?
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Sensing and signaling of DNA breaks and their repair through homologous recombination.
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What do PARP drugs do?
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These drugs inhibit PARP, which is an enzyme involved in non-homologous end-joining. BRCA1-deficient cells rely more on this kind of DNA repair than cells with BRCA1.
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What do anti-angiogenesis inhibitors inhibit?
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VEGF-VEGF Receptor signaling (ex: Avastin)
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What are the two older examples of molecularly-targeted therapy?
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Folate antagonist for childhood leukemia (aminopterin) and SERMs (selective estrogen receptor modulators) for hormone-responsive breast cancer.)
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What are some recently approved molecularly-targeted therapies?
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Imatinib (Gleevec) for CML,
Erlotinib (Tarceva) for small cell lung cancer, Bevacizumab (Avastin) for colon/renal cell/breast CA, and Rituximab (Rituxan) for Non-Hodgkin's Lymphoma. |
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What is ASCT?
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Autologous stem cell transplant, treatment for breast cancer, author admitted results had been fabricated.
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What is adjuvant therapy?
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Therapy given after surgery or XRT to patients who do not have detectable cancer but are likely to relapse.
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What is "biologic therapy?"
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IL-2, retinoids, angiogenesis inhibitors, etc; therapeutic agents that are not cytotoxic.
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What does the term "epigenetic" mean?
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Modification of the genome that does not change DNA sequence order (i.e. not a deletion, translocation, or point mutation.)
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What is in situ cancer?
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In situ means that there are malignant-appearing cells that do not yet show invasion of the basement membrane (malignant appearance, dysplastic behavior.)
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What does NED mean?
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No Evidence of Disease.
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What is a possible scenario for the genetic events leading to colon cancer?
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APC mutation, COX-2 overexpression, K-RAS mutation, DCC (loss of 18q), p53 mutation
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What are the differences between normal growth, early tumors, and late tumors regarding cell cycle stage?
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Normal tissue: mostly non-cycling cells, low growth fraction.
Early growing tumor: mostly cycling cells, high growth fraction. Late growing tumor: necrotic center, many non-cycling cells, hypoxia, relatively low growth fraction. |
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What is the TNM system?
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Describes spread of tumor.
T = extent of primary tumor (T0 to T4) N = extent of regional lymph node involvement (N0 to N3) M = denotes presence of metastatic disease (M0 or M1) |
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What do the Ts stand for in colorectal cancer?
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T1 = superficial tumor
T2 = muscle invasive tumor T3 = growth through muscularis propria T4 = adherent to adjacent organs |
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What are consolidation, intensification, and maintenance?
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Consolidation is chemotherapy repeated after a remission to solidify the remission and increase cure.
Intensification is use of a higher dose in remission to intensify the response. Maintenance is used in some diseases to increase the disease-free interval. |
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What is synthetic lethality?
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Two genes are in a synthetic lethal relationship if a mutation in either gene alone is not letal but mutations in both cause death of the cell.
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What are the three phases of drug development?
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Phase I = toxicity ascertainment
Phase II = efficacy ascertainment Phase III = comparison to standard therapy |
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What is Gompertzian growth of tumors?
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?
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What are some examples of oncogenes?
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cyclin D1, K-RAS, c-MYC, akt
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What are some examples of tumor supressor genes?
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p16, RB, p53, PTEN, BRCA1
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What are the requirements for combination regimens?
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Different mechanisms of action,
Non-overlapping toxicities, and Dose and time "intense" |
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What are some mechanisms for drug resistance?
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Overexpression of drug metabolizing enzymes,
overexpression of drug targets, expression of drug efflux pumps, increase in DNA repair, and transport defects. |
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What are the stages of the ECOG performance status?
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PS0: no symptoms or limits from disease.
PS1: restricted but able to carry out light work. PS2: capable of all self-care but incapable of work. PS3: capable of limited self-care, confined to bed/chair more than 50% of waking hours. PS4: completely disabled, can't carry out any selfcare. PS5: dead. |
