2.18 The Hallmarks of Cancer Flashcards
Folic acid analog that kills rapidly dividing cells in the bone marrow
Aminopterin
Used in chemotherapy and obtained brief, tantalizing remission in acute lymphoblastic leukemia
Aminopterin
Disease of the cell
Cancer
6 Hallmarks of cancer
Self-sufficiency in growth signals Insensitivity to anti-growth signals Evasion of apoptosis Limitless replicative potential Sustained angiogenesis Tissue invasion and metastasis
Ability to proliferate even in the absence or low levels of signals from the outside world tat tell the cell to proliferate
Self sufficiency in growth signals
Cell’s options and growth factors
Survive
Divide
Differentiate
Die
Abnormal proliferation can come from __ and ___
Mutation
Increased expression of growth factor receptors
In breast cancer, there is an increased expression of __
HER2 gene on chromosome 17
Infiltrating tumor cell nuclei are highlighted by the __ fluorescence in FISH
Blue
Most cells are in the G0 state and are kept there by ___
Antiproliferation signnals
Autosomal dominant disorder
Rare cancer of the retina
Gene responsible is found in chromosome 13
Retinoblastoma
In retinoblastoma, theis codes protein that keeps cells from proliferating
Rb gene
Stop cell division in response to internal or external signals
Tumor suppressor genes
Involved in transcription, DNA repair and cell-to-cell recognition
Tumor suppressor genes
Key regulator of cell cycle arrest through the cyclin-CDK complex
p53
Gene that reduces the probabiilty that a cell in a multicellular organism will turn into a tumor cell
Tumor suppressor gene
Secreted by a fungus that can grow in certain food, known carcinogen
Aflatoxin
Produces a protein that has the ability to bind p53 and prevent it from interacting effectively with its target genes
Hepatitis B
Integrity of the cell’s genome is monitored by the transcription factor ___
p53
Deletion or mutational silencing of __, __ or __ results in unregulated cell growth with an increased risk of tumor formation
p53
RB
INK4
Certain number of cell divisions that a cell is allowed to have before it stops
Hayflick limit
Shorten after each cell division
Telomeres
Repairs telomeres, can reverse the shortening and help immortalize cells
Telomeraase
Making blood vessels from pre-existing ones
Angiogenesis
Angiogenic factor (AF) binds to ___, which leads to intracellular signaling
Endothelial cell (EC) receptor
Important for triggering metastasis
Neovascularization
Antibody that binds to vascular endothelial growth factor, which doesn’t kill cancer directly, but it prevents angiogenesis of tumors
Avastin
Fluoropyrimidine-based antineoplastic agent
Monoclonal antibody
Avastin
Crucial in identifying aggressive cancers versus those that are not aggressive or even those that are benign or malignant tumors
Metastasis
Local metastasis
Intravasation
Cancer spread to certain type of tissues
Metastasis
3 possible fates of metastasized cells
New colony
Cell Death
Dormancy
Apoptosis induced by the lack of correct cell/ECM attachment
Anoikis
Enzymes that degrade the ECM play crucial roles in invasion and metastasis, and high expression is correlated with (better/poorer) prognosis
Poorer
Coping strategies of cancer cells
Angiogenesis Produce more growth factors Recruite neighboring stromal cells Disguise from the immune system Cell tries to find a friendly environment
Able to get away from home tissuue
Metastasis
Emerging hallmarks
Avoiding immune destruction
Deregulating cellular energetics
Altered/missing MHC (major histocompatibility complex)
Avoiding immune destruction
Warburg effect
PET scanning to track glucose
Deregulated energetics in cancer
Where you see a lot of anaerobic activity happening compared to normal aerobic activity
Warburg effect
In tumor cells, glycolysis tends to go __ or __
Anaerobic;
Truncated TCA cycle where acetyl-CoA is used as a bulding block for proliferation
Enabling hallmarks
Genomic instability
Tumor promoting inflammation
Chronic inflammation, may lead to DNA damage due to production of mutagenic chemicals by cells of the immune system
Tumor promoting inflammation
Reactive oxygen species
Tumor promoting inflammation
Product of applied natural selection
Cancer
Can be used for myelodysplastic syndromes
DNA demethylation agents
Code for cell proliferation
Oncogenes
Growth promoters (not necessarily cancer gene)
Oncogenes
Gains-of-functions are associated with __
Oncogenes
Loss-of-function mutations are associated with __
Tumor suppressor genes
Normal gene that encodes a protein that regulates cell growth and proliferation andt that can be mutated to become a cancer-promoter oncogene
Proto-oncogene
Protective and loss of their functions contributes to cancer
TSG
True or false
Some miRNAs may become oncogenes or tumor suppressors by affecting the balance between normal cell cycling and cell death
True
Inherited mutations
Inherited in the germ line from the parents
Germ-line mutations occur in all cells of the individual
Germ-line mutation
Occur in one’s lifetime
Somatic mutation
Biggest RF for cancer
Age
A lot of people have this certain type of muation
Common Variants
Have low penetrance
Common variaants
Higher risk than normal
CHEK2 1100delC is associated with increased breast cancer risk
Rare variants
Have moderate to high penetrance
Rare variants
Presence of Rb gene will most likely lead to retinoblastoma
Rare variants
Proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder
Penetrance
Standard adjuvant therapy in breast cancer focuses on __ and __
Proliferation
Apoptosis
True or false
Every cancer is different
True
