Targeted Therapy for Lung cancers Flashcards
A patient comes to your office complaining of a rash.
The patient has a history of cancer and you believe that the rash could be caused by a drug she is taking for her cancer. This drug works by inhibiting what?
This patient is most likely taking Erlotinib which inhibits EGFR signalling by binding to the ATP binding site of the tyrosine kinase domain and blocking a variety of signalling cascades and celular proliferation.
Erlotinib is metabolized in the liver by CYP3A4, so there are many drug-drug interractions. Other side effects include diarrhea and pulmonary toxicity
One of your cancer patients comes to the office for a check up. Because you’re a great doctor, you have the nurse take the vital signs and his HR is 50. This patient’s bradycardia is likely a side effect of what medication?
What is the target of this medication?
This patient is most likely taking Crizotinib.
Crizotinib inhibits multiple kinases including ALK, ROS-1, and MET,
The fusion of what two proteins found on chromosome 2p encodes for a constitutively active kinase.
What drug targets this rearrangement?
The fusion of ALK and ELM4 encodes a consttutively active kinase with transforming capacity. The protein activates survival and proliferation pathways like Ras-Mek-Erk and the PI3K/Akt cascades.
Crizotinib targets this kinase and inhibits its downstream effects
What are the clinical indications for Crizotinib?
late-stage NSCLC that has
ALK gene rearrangement
or
ROS-1 gene rearrangement
What are other side effects of Crizotinib?
cardiac toxicity (QT prolongation, bradycardia)
pulmonary toxicity
hepatotoxicity
visual disturbances (blurred vision, diplopia, photophobia, and visual impairment)
Your cancer patient comes in to the office because of a cut on his leg that “doesn’t seem to be healing.”
What is the target of this drug
This patient is most likely taking Bevacizumab- a VEGF inhibitor.
Bevacizumab is contraindicated for use in what type of cancer?
Squamous cell carcinoma because it can cause serious pulmonary hemorrhage
Side effects of Bevacizumab:
Black Box
Other:
Side effects of Bevacizumab:
Black Box: GI perforation, Hemorrhage, and wound dehiscence
Other: Arterial thromboembolic events, Heart Failure, Hypertension, Hypersensitivity (including anaphylactic reactions) necrotizing fasciitis
What is the role of PD-1 in cancer?
PD-1 is a protein expressed on T-cells cells that interacts with PD-L1 on APC cells that acts to “turn off” the T-cell and prevent it from attacking other cells in the body.
In Cancer patients, PD-1 and PD-L1 are over expressed which inhibits the anti-tumor effect of the T-cells (the body doesn’t fight the cancer)
What is the MOA for Pembrolizumab?
(“-umab” are humanized monoclonal antibodies). The Ab binds to and blocks the PD-1 so it doesn’t interact with PD-L1 and “turn off.” This allows the immune system to target and destroy cancer cells
What is the DOC for melanoma and metastatic NSCLC
Pembrolizumab
Pembrolizumab is the first line agent for NSCLC patients who are
PD-L1 expression (+)
EGFR, ALK, and ROS-1 (-)
If a patient with AIDS is diagnosed with a metastatic NSCLC that is EGFR, ALK, and ROS-1 negative, can you still use Pembrolizumab as a treatment?
Yes, you just use it with caution as it is a tretment that is regulating the immune system
