Initial analysis of drug-induced heterogeneity in cancer cell lines

Drug-induced heterogeneity of cancer cells is a known concept that is not well understood.

Heterogeneity is a common characteristic of cancer and describes how cancer cells of the

same tumour can show distinct morphologies and genetic phenotypes, due to an increased

cell cycle and thus elevated occurrence of mutations. The exposure of cancer to drugs is

thought to be a diver of heterogeneity leading to acquired-drug resistance. This is when a

cancer mass that was once sensitive to a particular drug is no longer effected by it and results

in treatment failure, leading to loss of life of the patient if no other treatments are available.

The problem with heterogeneity and acquired-drug resistance is they can’t be easily studied

due to the need for multiple and extensive biopsies of the patient’s cancer. Therefore the

only way to study the process of the formation of drug-induced heterogeneity is through

experimental investigations into model cell lines.

Here we attempt to standardise an adaptation protocol for the formation of resistant cell

lines, with the aim of creating a protocol that allows comparison between different cell lines

and different drugs. We also wish to better understand the formation of resistance in UKFNB-3

cell lines with the hope of later identifying cross-resistance with other drugs. Moreover,

we aim the better understand heterogeneity by establishing clonal cell lines of UKF-NB-3

and exposing them to a number of tubulin-binding drugs, with the aim of making

comparisons between the clones and other established clones with acquired resistance to a

number of drugs.

We found that repeated adaptation of cell lines to the same drug results in resistant

heterogenic sub-lines. We also concluded that exposure of cells to drugs of a similar

mechanism of action can lead to varying results.