I am testing compounds on the patient's primary cancer cells as well as a cell line. Generally, I see better activity in cell lines compared to primary cells. Surprisingly I am seeing the wonderful activity of few compounds in patient-derived primary cells but not in the cell lines. Could anybody please explain the possible reason for better activity in PDCs than cell lines?
PDCs are closer to relevant models than cancer cell lines. Many cancer cell lines are not what they are supposed to be (according to the NIH, many cell lines have been cross-contaminated, especially if obtained between labs) or they have mutated to not truly reflect the true physiology of the cells they are modeling, by erroneous cell handling. You should be happy with your results!
Primary cell cultures are very heterogeneous. It means, that if you treat primary cell culture with some drug you will have a stochastic effect depending on the mix of cells present. It is similar to the situation in vivo. When you produce cell line, you separate cells, you culture them and then propagate the cells, and cells that are able to thrive the best in in vitro cell culture form your cell line. Usually this is only a specific subtype of cells present in a primary tumor. So you can obtain interesting results, but your results can be skewed. If 90% of cells in primary tumor are sensitive to the drug and 10% of them not, and this 10% due to the additional mutation grow the quickest, then they can be chosen as a cell line to represent this kind of tumor. It is still relevant as these are the cells which are the most dangerous to the patient in the primary tumor, but the results of the drug treatment, its efficiency can be different than observed for a primary culture, representing most of the cell types present in primary tumor.
Primary cultures are considered to be very heterogeneous and may or may not respond the way it should. It depends on how the cells are isolated and cultured. Primary cells take some time to be adjust growing on culture conditions while Moreover cancer cells usually acquire lots of mutations and changes in their genome and can become chemoresistance over time.
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