Question

9. Rational Treatment of Cancer (16 pts total) You are a cutting edge oncologist who has treated a cancer patient with Ireesa. The patient went into remission for several years but their cancer has now come back. You also have a cancer research lab in which you study drugs like Ireesa. You are also in the process of applying to the FDA for approval for a new clinical trial but you must first answer the following questions: a) What type of cancer does your patient have (give the most likely scenario)? (1 pt) b) What mutant gene/protein was Ireesa targeting? Is it an oncogene or tumor suppressor gene? (2 pts) c) What is the most likely explanation for the resistance to Ireesa? (2 pt) d) How would you go about proving that your hypothesis in (c) is correct? Hint: you still have some of the original tumor taken from the patient before being given Ireesa. (3 pts) e) You now want to directly target the gene (not the protein, that's what Ireesa targeted) and knock down its expression. How would you go about doing this? Name the technique you would use (2 pts) f) How will you deliver the treatment in (e) to the patient, keeping in mind that you are a cutting edge MD PhD and always like to use the newest techniques (2 pts) g) How will you determine whether you were successful in knocking down the expression of the target gene in the tumor? (2 pts) h) Even though you managed to knock down the target gene, several months later, the tumors start growing back, even more aggressively this time. This time you decide to find out what additional genes are activated in this tumor and are driving its proliferation. Time is short and you must look at all the genes at once. What technique will you use? (2 pts)

Answer 1

1. The type of cancer the patient in this non small cell lung cancer. This type of cancer starts with the cells of the lungs becoming abnormal and with the growth and progression of the tumor, it starts to spread across different parts of the body. 80 to 85% of lung cancers are non small cell lung cancer.
2. The drug tends to target tyrosine kinase inhibitor and hence the IREESA targets the gene for the tyrosine kinase and hence prevents it from expression. It targets the tyrosine kinase and prevents the growth of the cancer cells. The IREESA drug basically blocks the signals that are sent by the tyrosine kinase and hence helps in preventing cancer. IREESA hence blocks the epidermal growth factor receptor which is observed to be overexpressed in the tumors.
3. There are many cancerous growth which are found to be resistant against IREESA and this is due to presence of certain secondary mutations like T790M and C797S and hence it leads to activation of other signaling pathway. Due to the mutations found in the tyrosine kinase or the EGFR to which the drug binds, it prevents the drugs from binding and hence become resistant to IREESA.
4. The hypothesis that due to the mutations, the cancer become resistant to IREESA has been proven through a lot of experiment where the secondary mutations appeared. In an experiment, there were patients who were found to have developed a resistance against IREESA and this was found to occurrence of mutations within the EGFR gene. It was found that tumor continue to grow despite repeated therapy and hence it was found that additional mutation in EGFR gene strengthens the drug resistance.