Precision medicine is tailoring patient treatment based on the genotype of a patients individual tumor associated antigens and tumor specific antigens (neoantigens). In recent years, clinicians have faded away from one size fits all therapeutics, and have now began to rely on personalized medicine in order to identify which medication will work best not only for the type of cancer a patient has, but the genetic makeup of each individual tumor. Currently, researchers will perform a combination of Next Generation Sequencing (NGS), Whole Exome Sequencing, and proteome identification in order to map out the underlying genetic causes and biomarkers of a patients cancer. However, directly associating functionality with even the most advanced bioinformatics is extremely difficult, and to lead to a large number of missed markers and false positives. In order to circumvent this issue, researchers have begun performing functional characterization of patient tumors, by taking small biopsies and growing them in vitro, in order to determine their direct response to various treatments.
One formulation of these cancer cells, are known as organoids, or three-dimensional clumps of tumor cells which are able to grow independently. For the past decade or so, these organoids have been used to research specific types of cancer, however, it is not until recently that they have been generated from individual’s tumors for personalized approaches. A paper published in science from 2018 demonstrated that numerous patient derived organoids from the same cancer type, exposed to the exact same treatment, responded completely differently, and correctly predicted if a patient would note (100%) or would (90%) respond to the treatment.
Compared to traditional 2-D cultures, these organoids better show complete tumor heterogeneity, as many 2D cultures are a small subset of cancer cells which are able to survive in standard cell culture conditions. Therefore, three-dimensional organoids are able to reflect a sampling of an entire tumor, rather than a select subset. They also take much less time to develop compared with mouse xenografts, and therefore can be used on a larger scale in a faster timeline to identify if a therapeutic will be affective for a specific patient. Organoids can also be generated through a novel automated system created by Dr. Soragni from the David Geffen School of Medicine, which is able to grow organoids taken directly from ovarian cancer cells extracted during standard surgical tumor biopsies. This method saves a substantial amount of time, as primary cell lines do not need to be grown from patient tumor samples, as well as avoiding issues with media changes and introducing reagents directly to the organoids. Using the new system, Soragni and her colleagues tested two concentrations of 240 different kinase inhibitors in thousands of tumor organoids derived from four patients.
Current research is enhancing the organoid culture methodology in order to better recapitulate the tumor microenvironment. With the positive outcomes organoids have done for precision medicine, it is only a matter of time before they are used for personalized medicine as well to better identify patient specific tumor biomarkers and save many more lives.
