Cancer is a complex disease that causes uncontrolled division of abnormal cells completely distinct within each patient. Now, instead of looking at individual genetic mutations in isolation, this innovative approach allows scientists to create whole models with an incredible degree of variation.
“Patients not only acquire different mutations, but they acquire combinations, so you have to model really faithfully to understand what is happening. Our work provides proof-of-concept for new models in which we can test numerous genes and mutations simultaneously, sometimes one by one, sometimes combinations of the different mutations”, said Kwon-Sik Park from the University of Virginia School of Medicine and the UVA Cancer Center.
Along with Dong-Wook Kim and other fellows from the Department of Microbiology, Immunology and Cancer Biology, he has been busy studying the collective effect of these alterations and trying to better mimic the disease in the hope of providing a more complete picture. So far, the team managed to demonstrate their method by creating a model of small-cell lung cancer, the most aggressive form of lung malignancy.
By using CRISPR, a revolutionary gene-editing system, the researchers were ableto show that a common mutation in the CREBBP gene actually plays an important role in the development of cancer. Typically an anticancer agent, but when altered, it promotes tumor growth.
“Those particular cells become mutated by the carcinogens from smoke. Normally, this lost cell-cell contact would prompt cells to die through a process called programmed cell death, or apoptosis. However, if the same cells acquire additional mutations in other critical tumor suppressor genes such as RB and P53, as is frequently the case in [small-cell lung cancer], then instead of dying, they survive and continue to expand”.
The ability to map these molecular changes can greatly influence the way we conceptualize the fight against cancer and is expected to lead towards new strategies for stopping its formation and spread.
“By understanding how the disease actually arises and the key players in the disease we can design strategies for detection and prevention as well as treatment”.