Question

As a new targeted anti-cancer drug ‘FCIC-17’ enters Phase III clinical trials, it is determined that the drug requires hepatic activation in order to elicit a therapeutic effect. Further studies identify that the sole enzyme involved in the activation of this drug is CYP2C19.

Questions:

a) Select ONE specific factor (from the categories environmental, genetic or physiological) that may contribute to inter-individual variability in the activation of ‘FCIC-17’, and explain the potential consequences of this variability in terms of treatment response and tolerability. (250 words; 5 marks)

b) Briefly discuss how this variability may be controlled for in clinical practice. (150 words; 3 mark)

Answer 1

A) In today's world we are surrounded by things which has a potential to cause cancer including the environmental factorsbut still cancer depends a lot on the hereditary background of a person.Genetic background have strong association with different type of disease progression.People having mutations in genes which play major role in tumor suppressor and cell cycle,that is oncogenes will show a much more aggressive tumor growth as compared to those that have an indirect role to play.In terms of treatment, genetic biomarkers are commonly used to determine the type of treatment required by the patient and sometimes even to predict relapse cases.It also affects the clinical heterogeneity, clonal selection, and metastasis rate of a cancer.For example in this the enzyme CYP2C19 is required for suitable activation of the drug FCIC-17,but if a person possess a genetic defect such that the enzyme is misfolded or degraded or rendered inactive by any means then this therapy will be absolutely futile for that patients.Also if the person has high instability, means greater mutation rate than they might grow tolerant to this therapy by activation of some alternate pathway such that this drug has less or no effect,even if this happens for a small portion of cell of total tumor still this resistant population will proliferate and form a tumor.There are innumerable examples like this which proves that genetics plays an important role in cancer treatment and tolerance.

B) Unfortunately we cannot completely controll the impact of gentic factors on variability of disease treatment,but targetting defects which are more genralized and covers most of tha cases provides some relief. Also during preclinical studies people should be divided in groups on the basis of their trail outcome and in future patients with similiar genetic conditions should be considered for treatment accordingly.