Week 14 Flashcards
Role of PARP inhibitors
PARP inhibitors kill cancer cells with defective Brca gene
Function of brca
Recombination mediated double strand break repair.
Role of PARP protein
PARP [Poly (ADP ribose) polymerase] proteins are involved in repairing single strand breaks.
In absence of PARP, what happens?
In absence of PARP, BRCA (BReast CAncer) can compensate. The WT cell will detect that they don’t have a single strand repair pathway to use, so they will introduce another lesion so that the BRCA pathway can be induced and the break fixed.
Why does DNA damage to cancer cells result in permanent damage?
- Cancer cells have mutated away their BRCA genes.
- If a cancer cell were to have a single strand break and were exposed to PARP inhibitors, now the PARP pathway cannot be used to fix the break.
- It also does not have the BRCA pathway, so it has no way to repair that break.
- This results in permanent damage that it cannot overcome.
Cell targets of drugs that have been developed to target PARP.
Both cancer and WT cells.
Immune therapy for cancer
Because cancer cells have a lot of mutations, they make proteins with novel variants. The immune system recognizes these antigens as foreign and targets them.
What type of cell targets cancer cells in immune therapy?
A T-cell detects that the cell is expressing a foreign variant of a protein and infer that the cell is infected and will target it for destruction.
Why does antibody therapy for cancer sometimes have serious side effects?
Antibody therapy can neutralize immunosuppressive signaling pathways, unleashing T cell attack on cancer cells. Can have serious side effects.
Role of PDL1 system
Check and balance built into the immune system to ensure proper targeting.
How does the PDL1 system work?
The immune cell has a receptor for PDL. When PD1 is activated, it inhibits the T-cell response.
Cancer cells and PDL1
Normal cells will not express PDL1 while cancer cells overexpress PDL1.
Treatments that affect PDL1
There are antibodies that have been developed against PDL1.
Can block the function of PDL1 and PD1.
CAR-T
Chimeric antigen receptor T-cell therapy
How does CAR-T work?
The mutant variant (antigen) makes its way to the cell surface, and then an immune cell tries to recognize the mutant variant. However, sometimes there are not enough immune cells or they do not have the correct receptor.
Can engineer immune cells in the lab–this is the basis of the therapy.
Characteristics of the innate immune response
- Most cell types capable of mounting an innate immune response
- Innate immunity against pathogens is hardwired
- Fast–minutes to hours to days
- Provides short-lasting protection
- Ancient
Characteristics of the adaptive immune response
- Response mediated by specialized cells called lymphocytes, a subgroup of white blood cells (leukocytes)
- Adaptive immunity against pathogens is acquired.
- Slow–days to weeks
- Provides long-lasting protection
- More recent invention
What type of receptors are Toll-like receptors (TLR)?
A pathogen recognition receptor (PRR).
Structure of TLRs
Toll-like receptors form a dimer whose substrate is the ligand double-stranded RNA.
What happens when TLRs detect double-stranded RNA?
They will elicit an immune response. Why? Because our bodies do not have double-stranded RNA–it is a foreign molecule (sometimes found in viruses).
Pathogen-associated molecular patterns (PAMPs)
Pattern recognition receptors (PRRs) in host cells recognize conserved features of pathogens called pathogen-associated molecular patterns (PAMPs) to activate innate immune response
Effect of PRRs
PRRs induce a transcriptional program that fights the infection in the infected cell. PRRs also induce the infected cell to secrete cytokines that attract immune cells.
