Novel cancer treatments

Question 1

What are examples of targeted therapy and what does it treat?

Answer 1

BRAF-melanoma
ckit/PDFGR-GIST
EGFR-adenocarcinoma, lung cancer

Question 2

Are the above targeted therapies intravaneous or tablets?

Answer 2

Tablet

Question 3

Examples of immunotherapies and what do they treat? Are they intravaneous or tablets?

Answer 3

provenge- prostate cancer
t-vec-melanoma
Checkpoint inihibitors for renal, head and bladder cancer

Question 4

Why have targeted and
immunotherapies been
developed?

Answer 4

Because chemotherapies are toxic to rapidly dividing normal cells affecting bone marrow, GI mucosa, skin, hair and don’t work on every cancer type.

Question 5

What do targeted therapies target? What’s rationale behind it?

Answer 5

Overexpressed receptors or signalling pathways. Tumour cells are reliant on these pathways or receptors so blocking it will kill the tumour

Question 6

What’s the problem with using vemurafenib to treat melanoma? How did this happen? What are the side effects?

Answer 6

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

Question 7

What is a more effective drug than vemurafenib monotherapy and why? What are the side effects?

Answer 7

dabrafenib and trametinib combination therapy because it targets both MEK and raf decreasing activity of the signalling pathway.
Less cutaneous toxicity, cardiac damage, pyrexia

Question 8

Which exon mutations in c-kit has the highest response when treating with imatinib? How about wildtype c-kit?

Answer 8

exon11 and then exon 9

no response

Question 9

What does imatinib target?

Answer 9

ABL kinase,BCR ABL fusion, c-kit, PDGFR

Question 10

What toxicity is associated with imatinib?

Answer 10

Fluid retention, nausea, fatigue, rash, diahrrea

Question 11

What kinds of resistance mechanism are there and give an example of each?

Answer 11

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

Question 12

Where does mutations occur in EGFR? And what subpopulation is this seen in?

Answer 12

Catalytic domain

Adenocarcinoma, non smokers, women, asians

Question 13

What is the 1st line of treatment for lung cancer patients with EGFR mutations? How about the patients without EGFR muations?

Answer 13

Gefitinib

Carboplatin plus paclitaxel

Question 14

What are the side effects of EGFR treatment?

Answer 14

rash,diahrrea, nausea, anorexia

Question 15

What’s the problem with EGFR treatment?

Answer 15

Primary mutation
Secondary mutation- T790 mutation which increases ATP binding
Activation of other suvival pathway-MET

Question 16

What’s the rationale for using immunotherapy?

Answer 16

Spontaneous regression, abscopal effect, response to IL-2&interferon

Question 17

What’s the first line of treatment for melanoma? What’s the perks and downsides of using this? How to treat the porblem?

Answer 17

pembroluzimab monotherapy and ipilumimab/nivolumab
No neutropenic sepsis, oral mucositis,hair loss
autoimmunity, with immunosupprssion steroid

Question 18

What part of the immune cycle does ipilimumab target?

Answer 18

the priming and activation of t-cells at the lymph node

Question 19

What is a better substitute to ipilimumab and why?

Answer 19

nivolumimab and pembrolizumab, because they work at the tumour site therefore less toxicity(more specific)

Question 20

What happens if you combine both nivolumimab and ipiliumimab ?

Answer 20

It is slightly more better than nivolumimab monotherapy but the toxicity is substantial(50-60% grade 3-4 toxicity)

Question 21

What’s the objective response of the combination treatment?

Answer 21

57.6%

Question 22

What is the prognosis of lung cancer patients treated with pembrolizumab?

Answer 22

Hyperprogression-progression at a rapid rate compared ti before treatment

Question 23

Who to give nivolumab monotherapy and who to give combination therapy(nivolumab and ipilumimab)?

Answer 23

PDL1 positive tumours give nivolumab monotherapy but PDL1 negative tumours give combination therapy