Signaling networks activated in lung cancer cells yield new drug targets
New published research funded by UALC
Personalized, targeted therapies can offer prolonged survival and fewer side effects for patients whose tumors have specific genetic alterations. However, most patients will eventually become resistant to treatment with targeted drugs. Finding new targets will help us to develop additional drugs in our arsenal against lung cancer.
Dr. Il-Jin Kim, funded by Uniting Against Lung Cancer, and the team at the University of California, San Francisco are investigating the changes that take place in lung cancer cells that contribute to this resistance, and have published their findings in Nature Communications.
Targeted therapies focus on one specific genetic mutation found in cancer cells. However, Dr. Kim and his team are taking a wider view, investigating networks of genes and proteins working together that contribute to cancer growth. Looking at 92 matched samples (comparing lung adenocarcinoma cells with normal cells from the same patient), they were able to analyze the changes in many genes and organize them into networks controlling different cellular functions.
Lung cancer cells showed changes in many key networks controlling structural and functional components of the lung, the machinery of cell division, and inflammation. Digging deeper into these networks, the team was able to identify key genes that could be targeted to halt cancer growth (akin to taking out the workers in the middle of an assembly line), including VRK1. Preliminary tests showed that targeting VRK1 could increase the sensitivity of lung cancer cells to other targeted drugs.
By mining vast gene expression networks, Dr. Kim and his team hope to expand the pool of therapeutic targets in lung cancer while avoiding severe toxicity to normal cells.
“Many cancer researchers put tremendous time and money into finding new tumor targets by analyzing tumor samples. Though many are very effective, most of them turn out to be very dangerous to non-tumorous tissues as well and despite all the hard work, are unusable,” said Dr. Kim. “Our systems genetics results let us select tumor-specific drug targets beforehand, helping us to develop a smarter, safer arsenal in the battle against cancer.”
“If we can identify tumor-specific targets before spending decades and millions of dollars on the wrong targets, we can dramatically reduce time and costs of drug development, getting safe and effective treatments to patients in need,” added Dr. Kim.
This was his first grant awarded as the principal investigator of his lab at UCSF. “It was Uniting Against Lung Cancer who believed in me. With their help, my lab has been able to discover several novel lung cancer drug targets and markers, and published nine papers since last year. We currently have several projects on going, and I hope to continue in our advancements against cancer.”