Resistance to Tarceva, step by step
Yesterday, I checked the lung cancer Tarceva sensitive cells, under treatment to Tarceva to generate resistance and I'm really glad that I am reaching the limit of the micro molar resistance.
That might seem a little bit esoteric but think that I have two cell lines sensitive to Tarceva (a TKI, tyrosine kinase inhibitor, that blocks uncontrolled activity of EGFR). These cells were sensitive to levels of 5-30 nano molar concentration of Tarceva. By exposing them to Tarceva over time and increasing the dose every 5-7 days now they can resist doses of 500-600 nano molar Tarceva. It's been almost 3 months since I started with these treatments.
And I have isolated mRNA from each cell at every new dose so I when I'll reach the maximum level of tolerance I'll have the history of this resistance documented through mRNA. mRNA is the functional genetic information present in the cell at every given moment.
So, next week I will increase the doses from 480 nano molar and 640 nano molar to 1000 nano molar (or 1 micro molar) and 1200 nano molar (1.2 micro molar).
It's a huge step because I am approaching the maximum reported in other cases. I am getting close to get an interesting picture of this process of resistance to therapy in lung cancer cells. A picture that, I hope, mimics what happens in real life when a patient is exposed to this drug, gets better and then gets worse again.
Having all these mRNA samples will allow to study the changes in processing of genetic information over time and over increases of the drug and see what is going on.