Novel cancer treatments Flashcards
(23 cards)
What are examples of targeted therapy and what does it treat?
BRAF-melanoma
ckit/PDFGR-GIST
EGFR-adenocarcinoma, lung cancer
Are the above targeted therapies intravaneous or tablets?
Tablet
Examples of immunotherapies and what do they treat? Are they intravaneous or tablets?
provenge- prostate cancer
t-vec-melanoma
Checkpoint inihibitors for renal, head and bladder cancer
Why have targeted and
immunotherapies been
developed?
Because chemotherapies are toxic to rapidly dividing normal cells affecting bone marrow, GI mucosa, skin, hair and don’t work on every cancer type.
What do targeted therapies target? What’s rationale behind it?
Overexpressed receptors or signalling pathways. Tumour cells are reliant on these pathways or receptors so blocking it will kill the tumour
What’s the problem with using vemurafenib to treat melanoma? How did this happen? What are the side effects?
It’s not that effective, MEK activation becomes more through another mechanism making the tumour more aggresive.
Diahrrea, fatigue, joint pain cutaneous scc, hyperkeratosis, rashes
What is a more effective drug than vemurafenib monotherapy and why? What are the side effects?
dabrafenib and trametinib combination therapy because it targets both MEK and raf decreasing activity of the signalling pathway.
Less cutaneous toxicity, cardiac damage, pyrexia
Which exon mutations in c-kit has the highest response when treating with imatinib? How about wildtype c-kit?
exon11 and then exon 9
no response
What does imatinib target?
ABL kinase,BCR ABL fusion, c-kit, PDGFR
What toxicity is associated with imatinib?
Fluid retention, nausea, fatigue, rash, diahrrea
What kinds of resistance mechanism are there and give an example of each?
Primary resistance-BRAF,ras,SDHB muations
Secondary mutations-reactivation of kit phosphorylation
interference iwth imatinib binding
dedifferentiation
activation of other pathway such MET
New mutations arising
Where does mutations occur in EGFR? And what subpopulation is this seen in?
Catalytic domain
Adenocarcinoma, non smokers, women, asians
What is the 1st line of treatment for lung cancer patients with EGFR mutations? How about the patients without EGFR muations?
Gefitinib
Carboplatin plus paclitaxel
What are the side effects of EGFR treatment?
rash,diahrrea, nausea, anorexia
What’s the problem with EGFR treatment?
Primary mutation
Secondary mutation- T790 mutation which increases ATP binding
Activation of other suvival pathway-MET
What’s the rationale for using immunotherapy?
Spontaneous regression, abscopal effect, response to IL-2&interferon
What’s the first line of treatment for melanoma? What’s the perks and downsides of using this? How to treat the porblem?
pembroluzimab monotherapy and ipilumimab/nivolumab
No neutropenic sepsis, oral mucositis,hair loss
autoimmunity, with immunosupprssion steroid
What part of the immune cycle does ipilimumab target?
the priming and activation of t-cells at the lymph node
What is a better substitute to ipilimumab and why?
nivolumimab and pembrolizumab, because they work at the tumour site therefore less toxicity(more specific)
What happens if you combine both nivolumimab and ipiliumimab ?
It is slightly more better than nivolumimab monotherapy but the toxicity is substantial(50-60% grade 3-4 toxicity)
What’s the objective response of the combination treatment?
57.6%
What is the prognosis of lung cancer patients treated with pembrolizumab?
Hyperprogression-progression at a rapid rate compared ti before treatment
Who to give nivolumab monotherapy and who to give combination therapy(nivolumab and ipilumimab)?
PDL1 positive tumours give nivolumab monotherapy but PDL1 negative tumours give combination therapy
