Summary: ChemoScreen offers a service to screen your compound for activity on proliferating chemo-resistant tumor cell lines. These cells have acquired resistance to a clinically-relevant chemotherapy drug through extensive exposure to the drug in vitro. Data from this test will indicate whether your compound is active on cells already resistant to the other anti-tumor drug. This information may be useful in selecting a hit or lead during preclinical development. Alternatively, during clinical development, knowledge about the compound's activity on cells resistant to a licensed drug or one in late stage development might help select a sensitive patient population for efficacy evaluation.
Screening Assays Details: There is a small number of licensed compounds and a much larger and growing number of compounds in development that have been designed to selectively interact with specific tumor-associated targets. Tumors will typically become resistant to a single compound (Compound X) as a result of the relatively high intrinsic genetic mutation rate of tumors and selection pressure by Compound X. Once resistant, the tumor will grow unless exposed to a different compound (Compound Y) that inhibits the function of a different target necessary for tumor development. This target might be one that is present in tumor cells prior to exposure to Compound X or, if the molecular lesion underlying resistance to Compound X is known, might be one that contributes to resistance to Compound X. In either of these scenarios knowledge of Compound Y’s target still does not necessarily mean Compound Y will inhibit the proliferation of those Compound X-resistant tumor cells at concentrations relevant to patient treatment. ChemoScreen’s test offers a method to determine whether Compound Y has activity on Compound X-resistant tumor cells. This valuable information should significantly decrease the risk of making a poor decision when considering further development of Compound Y.
Test validity: Resistance in vitro does not necessarily result in acquisition of the same genetic lesion(s) profile as would occur in a patient (refs). However, there are sufficient reports of there typically being common lesions to validate this approach (refs).