Cancer Chemotherapy Flashcards
Explain what cancer is and the usual presentation of it
Cancer is when abnormal cells multiply in an uncontrolled manner - which may lead to a large mass of abnormal cells, called a tumour. It can disrupt metabolic signalling, physiological functions, and lead to morbidity and mortality. A solid tumour doesn’t usually contain cysts, and they can be benign or malignant. They can go from a primary to a secondary site - metastasis.
Explain what differences between cancer cells and normal cells we can exploit in order to target them for therapy?
Uncontrolled growth of cancer cells - they have a greater demand for energy and anabolic substrates
Cancer cells have a less well regulated cell cycle and they duplicate DNA much more frequently, so we can target these processes.
What are the 6 Hallmarks of Cancer and the 4 Emerging Hallmarks of Cancer?
Resisting cell death - Use proapoptotic BH3 mimetics
Inducing angiogenesis - Use VEGF signalling inhibitors
Enabling replicative immortality - Use Telomerase inhibitors
Sustaining proliferative signalling - Use EGFR inhibitors
Evading growth supressors - Use Cdk inhibitors
Activating invasion and metastasis - Use HGF/c-Met inhibitors
Emerging :
Deregulating cellular energetics - Use aerobic glycolysis inhibitors
Avoiding immune destruction - Use anti-CTLA4 mAb
Genome instability & mutation - Use PARP inhibitors
Tumour-promoting inflammation - Use selective anti-inflammatory drugs
How does chemotherapy work?
Chemotherapy directly exploits the anabolic, replicative and metabolic processes of cancer cells, with the aim of selectively killing them via cytotoxic agents. A simple cytotoxic agent will kill normal cells, leading to unwanted side effects. If the tumour is too large, it needs to be operated on because the dose required would be too high, so operate and then chemo - debulking.
Describe the cell cycle
G1 is a growth phase, biosynthetic processes are high, number of organelles increases - prepares the cell for division. S phase is where DNA is replicated, and chromosomes are (forming sister chromatids) and biosynthetic processes are low. G2 is another growth phase, and the microtubules start to form the spindle, and the cell produces and assembles materials for mitosis. Mitosis then happens, followed by cytokinesis. G0 is a resting phase.
How is the cell cycle in cancer cells exploited in therapy?
For growth and metastasis, cancer cells need to progress quickly through the cell cycle. Therefore, we need to exploit this and target the cell cycle.
Explain what is meant by growth fraction and how it relates to cancer therapy
The growth fraction is the % of cells in proliferative vs resting phases at a given point in time. Chemotherapy which targets the cell cycle is effective for cancers with a large growth factor. Non cell cycle targeting chemotherapies are effective for both high and low growth fraction malignancies.
