Molecular Basis of Cancer Flashcards
How many mutations are necessary to transform a cell?
More than one–that’s why it takes a long time
The initial target of mutations is ___
A stem cell with self renewable capcity
Malignant tumors are monoclonal in origin, and are genetically ___ (heterogenous/homogenous) at clinical presentation
Heterogeneous–because of continued mutations and Darwinian selection
Mutations that affect genes that regulate cell growth are called _______, and others that affect genes not involved in cell growth are called ____
Mutations that affect genes that regulate cell growth are called driver mutations, and others that affect genes not involved in cell growth are called passenger mutations.
What is the most commonly mutated growth promoting gene in human cancers, and how does it occur?
RAS:
Due to a signal, inactive RAS becomes active RAS (GTP bound)
When active RAS, activates transcription through RAF -> MAPK , PI3K -> AKT, mTOR
when it’s mutated, it will be active regardless of growth factors
Dysregulation of ___ is checkpoint is common among all cancers
G1-> S checkpoint
What is Rb, and how does it matter ?
Rb is a growth inhibiting gene: controls the G1-> S checkpoint
CDK phosphorylates Rb, adn it relieves the G1-S checkpoint
Virtually every cancer has a mutation in one of which four classes?
RB
CDK4
Cyclin D
CDKN2 (p16)
How do growth inhibitors affect phosphorylation of Rb? What about growth promoters?
Promoters cause phosphorylation of retinoblastoma
Inhibitors prevent phosphorylation of Rb
Rb is the governor the cell cycle. What is the guardian of the genome? How does it operate?
TP53: maintains the integrity of genome
If there is DNA damage, it triggers p53 into action, so cell cycle is arrested (via CDK Inhibitor), expression of DNA repair genes, senescence, and if that fails then apoptosis
For metastasis via hematogenous process, what does it have to do?
adhere and invade basement membrane, go through extracellular matrix, intravasate, interact with host lymphoid cells, adhere to basement membrane, extravasation,deposit and growth in a new place.
A lot of different properties: so not likely to be just one gene will be found
If you use an inhibitory antibody to block CTLA-4, what does this do? How does this address some tumors?
It allows cytolytic CD8+ T cells (CTL) to engage B7 coreceptors, and therefore be activated.
Tumors hijack normal checkpoints of T cell activation, and therefore prevent T cell activation.
So you can use this antibody to treat cancer
If you use an inhibitory antibody to block PD-1 receptor , then what does this do?
It activates of CTLs
