A three-dimensional tumor-in-dish (TID) cell-based assay kit for cancer drug screening that closely replicates actual cellular microenvironments and, therefore, can determine which compounds to move forward for in vivo testing.
Despite numerous advances, one of the most fundamental challenges in cancer drug development is the extrapolation of safety and efficacy data from in vitro cell culture assays to animals. Positive findings from in vitro assays that don't manifest in later in vivo tests represent significant lost time in bringing therapies to patients. Therefore, developing an effective model system that better represents both normal and cancerous cells is imperative. In contrast to the current two-dimensional approach of culturing tumors in vitro (known as tumor-in-dish or TID), Dr. Anant has discovered a way to characterize, optimize, and standardize conditions for TID in a three dimensional spheroid culture along with the normal epithelial, fibroblast, and endothelial cells which creates the in vivo-like cellular microenvironments. The multicellular-type tumor spheroids are grown in cell culture media without any extra-cellular matrix components added. This is quite unique and vital for mimicking real human tumors. Recent observations by Dr. Anant's team and others have clearly indicated that data generated by 3D models is much closer to clinical expression profiles than by the 2D models.
Cancer drug development, personalized medicine, and studying tumor metastasis.
The unique combination of types and amounts of cells enables cancer cells to self-assemble in a three dimensional spheroid culture along with normal epithelial, fibroblast, and endothelial cells, which creates the in vivo-like cellular microenvironment. The tumor spheroids are grown in cell culture medium without additional extracellular matrix components. This is unique as it mimics the formation of actual human tumors. The kit may also include test compounds and methods for determining whether the test compounds inhibit, attenuate, prevent or reduce tumor growth, proliferation, size or metastasis. To date, the kit has been tested with success in colon cancer, pancreatic cancer, breast cancer, melanoma, ovarian cancer, medulloblastoma, and glioblastoma. It is anticipated that it will be of use in any solid tumor type.
This TID culture system provides an easier, reproducible and more reliable therapy testing system with very high potential to predict clinical efficacy. It can be used for high throughput screening of drugs in a short period of time with limited amount of drug. The kit also provides methods for analyzing the effects of hypoxia, core necrosis, therapy resistance, angiogenesis, invasion and metastasis in the tumor microenvironment.
This novel TID model has more promise for anticancer drug development than the 2D and 3D systems currently being used as it actually impersonates many aspects of the biochemical, morphological and pathophysiological situation in tumors such as hypoxia, core necrosis, therapy resistance, angiogenesis, invasion and metastasis.