cancer genetics- lecture 15 Flashcards
what is cancer?
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems
characteristics of normal cells
characteristics of cancer cells
-dont enter G0 (which tells them to stop dividing)
-escape checkpoint
-don’t arrest in cell cycle
hallmarks of cancer
sustaining proliferative signaling
never enter G0, always dividing
Cells have a receptor at their surface which, when receiving a growth factor signal from neighboring cells, initiates an intracellular cascade of signaling which leads to cell growth and division
Cells normally need this feedback from other cells to know when to divide, ensuring that proliferation happens in a coordinated manner
Cancer cells are able to divide even without receiving these signals which leads to an uncontrolled proliferation of these abnormal cells. It is often a mutation in the receptor’s gene that maintains a growth signaling cascade – even in absence of the signal. At each replication cycle, the mutation is passed onto the daughter cells. This uncontrolled proliferation could eventually lead to the formation of a mass which we call a tumor.
evade growth suppressors
In order to maintain homeostasis, along with growth factors, cells can also produce growth suppressors which act as a stop signal for themselves or on neighboring cells if they are growing in an uncoordinated fashion. However, cancer cells, stubborn as they are, happen to ignore these “anti-growth signals” just like a speeding car going through a red light. This, also contributes to continuous proliferation of the cancerous cells
activating invasion and metastasis
The sixth hallmark is also the event that most often leads to death: activating invasion and metastasis. At this stage, the cancerous cells not only invade neighboring tissues but also activate metastasis -which means these cells can now migrate through the blood and spread all around the body and eventually form new tumors in other locations. Therefore, it is difficult to locate them and provide focused treatment.
enabling replicative immortality
cells have a natural expiry date after which they are destined to die. some cancer cells overcome this expiry date and can divide indefinitely rendering them immortal. Henrietta Lacks was a patient who died of cancer in 1951, and a cancer cell line called HeLa was derived from her cervical cancer cells and this line is still being widely used in research today due to its immortality.
inducing angiogenesis
Cell growth and division require a lot of energy which is provided in form of nutrients and oxygen from the surrounding blood vessels. So, you would think that at some point, cancer cells would not have enough resources to divide endlessly, especially if they are packed up in a tumor. Well, cancer cells secrete molecules which stimulate blood vessel growth. This process is called angiogenesis and is the fifth hallmark of cancer. This creates a larger network of vasculature around and within the tumor and provides the cells sufficient nutrients and oxygen to keep growing. Angiogenesis is a vital process in development that is usually activated during wound healing, but microenvironmental changes cause it to be activated in cancer cells as well.
resisting cell death
So, these mutated cells are dividing without control, and as we saw in the previous video on cell death which you can watch on our channel, cells have an internal sensor to detect dangerous mutations, and initiate apoptosis to eliminate faulty cells through cell suicide. So you would think that these mutated cells would eventually die, right? Well that would be the ideal solution, however, the third hallmark of cancer is the resistance to cell death. Cancer cells often have a mutation in one of the signaling proteins leading to cell death, which helps them evade this fate.
oncogene
gene whose normal activity is to promote cell growth
mutations are dominant, gain of function promoting cell transformation
tumor suppressor gene
gene whose normal activity is to inhibit tumor progression
mutations are dominant, loss of function resulting in loss of cell cycle regulation
how we discovered oncogenes
examples of oncogenes
what genetic events can convert genes (proto-oncogenes) to dominantly acting oncogenes
MYC
ways to increase oncogenic MYC expression
1) genetic aberrations
2) transcriptional regulation
3) protein stabilization
RAS
bRC-ABL
two-hit hypothesis
hypothesis that most tumor suppressor genes require both alleles to be inactivated
main tumor suppressor genes
p53
BRCA1/2
APC
p53
The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way
how does p53 guard the genome
activates dna repair proteins if dna has sustained damage, arrests cell cycle, initiates cell death
brca 1/2
dna repair proteins
apc
what problems do cancer cells have with their dna?
aneuploid
Many cancer cells, such as this lung cancer cell, have extra or missing chromosomes. Around 90% of tumors have cancer cells with extra or missing chromosomes—a phenomenon known as aneuploidy. Despite this frequency, scientists have struggled to understand whether aneuploidy is harmful or helpful to cancer cells
how do tumors progress
role of telomerase in cancer cells
metastasis
the development of secondary malignant growths at a distance from a primary site of cancer.
why is cancer typically a late life disease
therapeutics of cancer
classes of chemotherapeutic agents
precision cancer medicine
drugs targeting epigenetic modification in cancer
