Cancer consists of >100 distinct diseases that manifest in ~200 cell types with diverse genetic/mutational etiologies. For the clinician this complexity is compounded by the fact that a single disease phenotype can result from multiple genotypes, each of which requires a unique approach to treatment (estrogen dependent/independent breast cancer being a primary example).
This complexity is necessitating a shift away from a “one size fits all” approach to cancer therapy, and movement towards personalized cancer medicine, where the goal becomes “the right treatment for the right person at the right time.” In the future, exhaustive molecular/genetic and cellular characterization of a patient’s diseased and healthy cells will predicate their treatment regimen. While the rate of progress towards this end is ever increasing, our ability to use biomarkers and patient-specific immunodynamic responses to decipher an optimal treatment program is currently lacking. Alternative assay technologies are therefore urgently needed. Towards this end, the ex vivo functional screening of chemo- and immunotherapies against a patient’s diseased cells may help physicians to empirically decipher optimal treatment regimens prior to actually administering them.
Last month, Lukas Bubendorf and colleagues at The University Hospital in Basel published an article in the journal PLOS ONE describing their development of an ex vivo assay geared towards personalizing cancer therapies. Critical to their approach was the type of patient-derived cells they chose to work with. They noted that though previous efforts in this field have provided some promising results, these assays “have not proved to be sufficiently reliable for clinical routine.” The authors suggested that this may be due, in part, to the fact that most of these studies used cells taken from solid tumors – which can be problematic due to contamination with non-tumor cells and because the process of tissue disaggregation can introduce artifacts. Because they are already adapted to growing in a liquid environment, do not depend on a stromal cell compartment, and are easy to purify, the authors suggested that carcinoma cells from malignant pleural effusions (MPEs) overcome these challenges.
Using an xCELLigence Real-Time Cell Analyzer from ACEA Biosciences, Bubendorf and colleagues quantitatively evaluated the ability of different general (cisplatin) and targeted (pemetrexed and erlotinib) chemotherapies to kill carcinoma cells isolated from the MPEs of pulmonary adenocarcinoma patients. They concluded that this approach “precisely reproduced the effect of clinically established treatments by standard chemotherapy and targeted drugs”, suggesting that this has the potential to directly help clinicians personalize the therapeutic regimens their patients receive.
The simple, label-free workflow of this xCELLigence RTCA assay, coupled with the quantitative killing kinetics it provides, make it a powerful platform for theranostics and basic research. “We believe this ability to rapidly screen a patient’s diseased cells against diverse (cellular, small molecule, antibody-based) mono and combination therapies will help personalized cancer therapy reach its full potential,” said Xiaobo Wang, ACEA’s chief technology officer.