1. Cancer Overview Flashcards
What are the 6 (Classic) Hallmarks of Cancer?
- Evasion of Apoptosis
- Self-Sufficiency in growth signalling
- Insensitivity to anti-growth signalling
- Tissue Invasion and Metastasis
- Limitless Replicative Potential
- Sustained Angiogenesis
What are the updated Hallmarks?
- Sustaining Proliferative Signalling
- Evading Growth Suppressors
- Avoiding Immune Destruction
- Enabling Replicative Immunity
- Tumour Promoting Inflammation
- Activating Invasion and Metastasis
- Inducing Angiogensis
- Genome Instability
- Resisting Cell Death
- Deregulating Cellular Energetics
Which therapy targets the sustaining of proliferative signalling?
EGFR Inhibitors
epidermal growth factor leads to DNA synthesis/cell proliferation
Which therapy targets the evasion of growth suppressors
Cyclin Dependent Kinase Inhibitors
CK regulates the cell cycle up to and including apoptosis
Which therapy targets the avoidence of autoimmune destruction by cancer cells?
Immune Activating Anti-CTLA4 mAb
On/Off switch for Cytotoxic T-Cells
Which therapy targets replicative immortality by cancer cells?
Telomerase Inhibitors (Telomerase prevents shortening of chromosome with each replication cycle)
Which therapy targets tumour promoting inflammation?
Anti-inflammatory Drugs
Which therapy targets the activation of invasion/metastasis?
Inhibitors of HGF/c-Met
HGF stimulation causes MET to initiate invasive growth
Which therapy targets angiogenesis?
Inhibitors of VEGF Signalling
Vascular Endothelial Growth Factor
Which therapy targets genomic instability and mutation?
PARP Inhibitors (Poly ADP Ribose Polymerase = Repairs single strand breaks in DNA, breaks more common in cancer, w/o repair, apopotosis will occur).
Which therapy targets the resisting of cell death by cancer cells?
Proapoptotic BH3 Mimetics
Bind to and inhibit the proapoptotics (prosurvival) (Bcl-2
Which therapy targets the deregulation of cell energies?
Aerobic Glycolysis Inhibitors
Cancer cell more dependent on aerobic ATP supply
What is Cellular Senescene?
A state of permanent cell-cycle arrest brought on by progressive telomere shortening and ultimately the activation of DNA damage responses. This limits the lifespan of mammalian cells and prevents unlimited cell proliferation. Linked to tumour suppression.
What is Autophagy?
It is a mechanism of chemoresistance which involves the formation of a double walled vesicle called an autophagosome that encapsulates and recycles cellular proteins and organelles.
How can autophagy promote cancer cell survival?
By a process known as “Cytoprotective Autophagy”. Which protects the cells against the cytotoxic stresses characteristic of tumour micoenvironments. Autophagy is the mechanism by which cells may avoid anoikis and metastasis may occur.
How can autophagy cause cancer cell death?
By a process known as “Terminal Autophagy” which initiates cell death either by the excessive cannibalisation of the cell or by inducing apoptosis.
What is Anoikis?
Anoikis is a form of programmed cell death induced by anchorage dependent cells detaching from the extracellular matrix (ECM). Anoikis is induced when there is a disturbance in normal cell-matrix signalling and other interactions controlling growth and survival.
How is Anoikis relevant to the development of cancer
Anoikis acts as a barrier to metastasis, preventing the survival of cells at inappropriate sites in the body. Resistance to Anoikis (caused by autophagy) is a form of chemoresistance.
What is the effect of hypoxia on tumour cells?
It causes an outgrowth in their vasculature and is associated with aggressive tumour behaviour including increased invasion, proliferation and metastasis.
What are the properties of hypoxic cancer cells?
Hypoxia is a form of chemoresistance involving low levels of o2 in the cells enviroment. It is associated with high resistance to radiation and chemotherapy (agents can’t travel through vaculature to site). Hypoxia can induce cellular senescence and cytoprotective autophagy.
What are the indications for the chemotheraputic agent Paclitaxel?
1st line in ovarian cancer, used in combination with carboplatin. 2nd line in advanced breast cancer.
What are exosomes?
Exosomes are cell-derived vesicles found in ECF.
Exocytosed by some cells, endocytosed by others.
Potential for Biomarkers
A way of spread pathologies cell-2-cell including cancer.
Micro RNA that can change transcription in target cells.
How might exosomes be used in cancer treatment?
Us patient tailored exosomes for the delivery of chemotherapeutics.
