Research published in Cell on July 7th has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors, and could be used to learn how tumors are likely to respond to new drugs, increasing the success rate for developing new personalized cancer treatments.
Scientists from the Netherlands Cancer Institute (NKI), the Wellcome Trust Sanger Institute (WTSI), and the European Bioinformatics Institute (EMBL-EBI) discovered a strong link between many of the mutations commonly found in patient cancer samples and sensitivity to specific anti-cancer drugs.
In this systematic, large-scale study, the researchers combined molecular data from tumors and cancer cell lines with drug sensitivity measurements. First, they identified molecular alterations strongly associated with cancer in more than 11,000 tumors across 29 different tumor types. Then they mapped these cancer relevant alterations onto 1000 cancer cell lines and determined whether these alterations explain the response of the cell lines to 265 anti-cancer drugs.
‘These data will help advance personalized cancer medicine by guiding researchers towards cancer specific molecular alterations that clearly associate with drug sensitivity. After further validation, this will allow the creation of clinical trials specifically tailored to well-defined subgroups of patients. Ultimately, this will inform the scientific community about potential anti-cancer drugs given a molecular profile of a tumor’, says joint first author of the study Dr Daniel J. Vis, research fellow at the NKI.
The researchers made two significant discoveries: First, the majority of molecular abnormalities found in patient’s cancers are also found in cancer cells in the laboratory. This means that cell lines are indeed useful models to identify the drugs that would work best for a given set of patients. Second, many of the molecular abnormalities detected in the patient cancer samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.
Previous studies have sequenced the DNA of cancers from patients to identify the molecular abnormalities that drive the biology of cancer cells. Researchers have also shown that large collections of cancer cell lines grown in the laboratory can be used for measuring sensitivity to many hundreds of drugs. However, this is the first study to systematically combine these two sets of information.
NKI group leader dr. Lodewyk Wessels, joint senior author on the publication, comments: “Our research shows that cancer cell line drug response can be predicted by combinations of molecular markers. We hope this information will ultimately help to design clinical trials that target those patients most likely to benefit from treatment.” (source)