Session 7 - Cancer and the Cell Cycle Flashcards
What are four different ways in which cancer can spread?
Local - Direct involvemnt of surrounding structures
Lymphatic
Blood
Implantation
What cancers spread via lymphatics?
Carcinomas and melanomas
What cancers spread via the blood
Sarcomas and Carcinomas
What cancers spread via implantation
Mechanical dump of tumour clump in peritoneum, ureters, CSF
What are two synonyms for primary therapy?
Curative treatment
Radical treatment
What is adjuvant chemotherapy?
Post-operativ treatment in a patient at high risk of microscopic metastases after removal of the primary tumour
What is neoadjuvant chemotherapy?
Primary treatment of patients with a clinically localised tumour. Can be used ot asses biological responsiveness of tumour and to reduce size for surgery.
What is always aimed for in neoadjuvant therapy?
PCR (pathological complete response)
What is palliative chemotherapy?
Not curative, symptomatic treatment only
In what malignancies is chemotherapy curative?
Haematological malignancies
Testicular cancr
What is fractional chemotherapy?
hemotherapy is used in very narrow range to kill cells in a fractional way. This means that chemo given in bursts with intervals, allowing healthy cell populations (bone marrow, etc) to recover while hammering down the malignant, poorly corrective cancer cells.
Give three types of cytotoxic agent?
Platinum compound
Anti-metabolites
Spindle Poisons
What do platinum compounds do?
Inhibit DNA synthesis via formation of platinated inter- and intrastrand adducts leading to inhibition of DNA synthesis
Name two anti-metabolites
Methotrexate
5-fluorouracil
What does methotrexate do?
Inhibits dihydrofolate reductase
What does 5-fluorouracial do?
Inhibits thymidylate synthase
What do spindle poisons do?
Once chromosomes aligned at metaphase plate, spindle microtubules depolymerize, moving sister chromatids towards opposite poles. Nuclear membrane re-forms and cytoplasm divides.
How do microtubule binding agents, such as spindle poisons, affect microtubule dynamics
Inhibit polymerization
Stimulate polymerization and prevent depolymerization
What is the aim of combination therapy?
Activity vs safety
Give two reasons to suggest why you would have two separate pharmacological agents in chemotherapy?
- Different mechanisms of action
- Different mechanisms of resistance
However, must take into account compatability of side-effects
Give a hormonal treatment in breast cancer other than tamoxifen
Aromatase inhibitors prevents Oestrogen conversion in fat from androgens – only work in post-menopausal women, as pre’s have functioning ovaries which will replace Oestrogen.
What is arbiaterone?
A drug which inhibits enzyme CYP17A1, which is crucial in conversion of pregnenolone and progesterone to testosterone
Name a drug which inhibits CYP17A1 and what is it used for?
Prostate cancer
Abiraterone
In what ways doe a cnacer cell differ from a normal cell?
- Lose contact inhibition
- Increase in growth factor secretion
- Increase in oncogene expression
- Loss of tumour suppressor genes
In what way do normal cells differ from cancer cells?
- Oncogene expression rare
- Intermittent or coordinated growth factor secretion
- Presence of tumour suppressor genes
Give an example of biologically targeted therapy
Philadelphia chromosome of chonic myeloid leukaemia
What is the philadelphia chromosome and what does it do?
- translocation of part of chromosome 9 to 22
- abl oncogene on 9 adjacent to breakpoint cluster bcr gene on 22, fusion leads to transcription of a protein and leukaemic transformation
- Provides target for anti-cancer therapy eg. STI 571
Give a treatment for CML?
Imatinib, Bcr-Abl tyrosine kinase inhibitor targets Philadelphia cells in CML and has massively increased survivability.
Give an antibody treatment for breast cancer
- Trastuzumab is a recombinant humanised IgG1 monoclonal antibody against the human
- epidermal growth factor receptor 2 (HER2).
- Antibody dependent cell mediated cytotoxicity (ADCC)
Give a biological therapy for colon cancer
Erbitux, an IgG antiboyd targets extracellular EGFR, altering signalling cascade
What is a VEGF trap?
Abflibercept – VEGF trap
VEGF romotes angiogenesis in vivo by inducing endothelial cells to invade collagen gels and proliferate to form capillary-like structures. The trap binds to VEGF and inhibits it.
