Cancer cells, which appear "same kind" rarely share the genetic alterations and defects. Therefore, a lack of similar response following treatment of cancer cells that appear "same kind" is not surprising. Further, alterations in the culture conditions (such as cell density) of cells impact the outcome.
As noted by Divaker Choubey, although cancer cells of the same kind may look identical, their regular phenotyping need to be performed to make sure they have not mutated or changed their identity on several passages or varying media conditions. Also it is well known that cancer cells can become resistant to several drugs just based on their exposure to various drugs and drug concentrations (the phenomenon by which drug resistance to cancer develops).
Well "Tissue is an issue" and so is tumor heterogeneity i.e. the bulk tumor cells might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment.
To be precise if estrogen receptor positive cells e.g mcf-7 and t47d were treated with same drug then why their IC50 value show much difference e.g 2UM for one cell line and 7uM for the other cell line?