Cancer Flashcards
What is cancer
Name of diseases in which abnormal cells divide in an accel/uncontrolled manner and have potential to invade other tissues
How are cancers organized
Tissue of origin and mutational status
Benign
Non-cancerous. Tumors can grow larger but lack ability to spread to neighboring tissues. Can still have bad health effects. Ex moles
Malignant cancer
Cells can divide uncontrollably and abnormally fast. Can also invade neighbor tissues. Cancerous
Metastasis
Spread of cancer from one tissue to another
6 hallmarks of cancer
- sustaining proliferative signaling
- evading growth suppressor
- activating invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
Apoptosis
Where a cell suffers some sort of damage and undergoes programmed cell death
Cancer cell evasion of apoptosis
Allows damaged cells to replicate. Genetic factors may be involved. P53 tumor suppression gene.
Self sufficiency in growth signals: normal vs cancer cells
Normal- req external GF in order to grow and proliferate
Cancer- dont require external growth signals to proliferate. If they do- can produce growth factors on their own
Insensitivity to anti growth signals
Normal v cancer
Normal- proliferation regulated and kept under control by anti growth signals
Cancer- insensitive to anti-growth signals
Evident even in vitro
Tissue invasion and mets
How cancer does this
Tumors send “pioneer cells” to invade adjacent tissues. Must 1st interact normally w existing local cells, then recruit cells from local tissue to make new tumors
Limitless replicative potential
Normal cells
Can only divide a certain number of times before they die. Telomere length determines division times. Shortens after each division, telomerase maintains them
Limitless replicative potential
Cancer cells
Can divide indefinitely even when p up DNA error due to inc in cell division
P53 tumor suppressor gene plays a role in limiting replication, turned off in cancer
Sustained angiogenesis
Role in Tumor
Tumor needs blood supply to grow in size and spread. Angiogenesis also provides tumor w o2 and nutrients
Tumor suppressor
A gene that protects a cell from becoming cancerous. Generally loss of function mutations cause these cells to be susceptible to becoming cancerous
Oncogene
Gene that puts a cell on the path to becoming cancerous. Begin as proto-oncogenes which have a regular physiologic function in the cell (r/t proliferation and differentiation). Begin to overexpress.
Tumor suppressor ex: p53
Classic role to prevent cells w dna damage from dividing. “Guardian of genome.” 50% of cancers have p53 mutations.
Two hit hypothesis
Why tumor suppressor genes become insufficient to prevent cancer. Both alleles for tumor suppressor gene need mutations for gene to lose function. Germline v somatic. Goes for majority of these genes (but not all)
Conventional cancer therapy
Radiotherapy
Surgery
Chemotherapy
Interfering w dna synthesis
Process
Folate must be taken up by cell and reduced to FH2 then FH4 by dihydrofolate reductase in order to produce nucleosides
How methotrexate works
Higher affinity for dihydrofolate reductase than does FH2. Prevents its reduction to FH4
Monoclonal antibodies
Block growth signals and stop new blood vessels from forming
New targeted therapies
Hormone therapy
Monoclonal antibodies
Tyrosine kinase inhibitors
Tyrosine kinase
Enzyme that removes a phosphate from ATP and attaches it to a protein, onto a tyrosine amino acid
Addition of a kinase starts a signal cascade that can lead to proliferation
Tyrosine kinase inhibitors do what
Prevent phosphorylation of tyrosine kinase target
BCR abl
Known as what
Occurs when what
Assoc w what
Philadelphia chromosome/translocation
When chromosome 22 has a specific translocation w chromosome 9, results in fusion gene known as bcr abl
Chronic myelogenous leukemia
Bcr abl
Contains what
Mutated form
A portion that codes for a tyrosine kinase
Tyrosine kinase is always signaling
Not all hyper proliferation caused by what, can also be caused by
What wouldn’t work
Mutated EGFR.
Mutated downstream effectors of EGFR
Cetuximab
