Cancer is caused by changes in the genetic material, or DNA, of normal cells. These changes accumulate over time, first turning normal cells into precancerous cells and then into cancer cells. Recent technological advances have made it possible to determine all the DNA changes that have occurred in an established malignant tumor.
The promise of precision medicine lies in the ability of researchers to devise treatment approaches that are specific to the genetic profile of individual patients and their tumors. However, predicting which drug, or drug combination, will be the most effective based on the genetic makeup of a tumor remains a challenge. This is largely because for most DNA changes, it is not known how they contribute to the cancer process or how they can be targeted by drugs. Therefore, there is an urgent need for new tools and technologies to investigate the consequence of all these DNA changes.
This Dream Team has developed a groundbreaking technology that allows tumor samples isolated from patients to be maintained and grown, in the laboratory setting. These growing tumors, which are called “tumor organoids,” provide an unprecedented opportunity to combine DNA sequence analyses with functional studies of tumors from individual patients. Importantly, these tumor organoids will allow studies of sensitivity and resistance to a large number of anticancer drugs in the lab.
The aim of the Sta Op Tegen Kanker Dream Team led by Hans Clevers, Ph.D., and Johannes Bos, Ph.D., is twofold. First, the Dream Team will establish a novel, genetically diverse "living biobank" of tumor organoids to test new cancer drugs as a first step towards tailored clinical trials. The team will focus on patients with pancreatic, prostate, or colon cancer. They will develop organoids of normal and tumor samples from 80 patients with each cancer type. After having determined the DNA sequence of each of these organoids, the researchers will test their sensitivity to 100 different drugs. Armed with this knowledge, the Dream Team will be able to classify tumors based on the drug sensitivity of tumor organoids and devise rules to match specific treatments with defined DNA changes in tumors. The team will then use this knowledge to perform additional preclinical studies of novel therapeutic strategies, including drug combinations.
By performing more thorough preclinical studies facilitated by this new technology, the Dream Team hopes to be able to design novel, more sophisticated clinical trials that will test treatment regimens tailored to a patient’s tumor. If successful, this Dream Team project has the potential to provide a true paradigm shift in our current approach to drug development, clinical trial design, and therapy.
Lodewyk F. Wessels, PhD, professor, Netherlands Cancer Institute, Amsterdam, Netherlands
Sir Michael R. Stratton, FRS, FMedSci, FRCPatH, director, Wellcome Trust Sanger Institute, Hinxston, United Kingdom