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How pharmacogenomic classification of tumors is driving forward precision cancer therapy

How pharmacogenomic classification of tumors is driving forward precision cancer therapy

22/03/2021
Posted by:

D. Hernandez


With cancer being a leading cause of death worldwide, responsible for 9.6 million deaths in 2018, the race towards effective treatment has been put on overdrive in the past few years. Cancer is a genetic disease - it is caused by changes to genes that control the function of our cells, mainly how the cells grow and divide. Genetic changes that put us at risk of developing cancer can be inherited from our parents, but they can also come about during our lifetime as a result to exposure to carcinogens, those dangerous chemicals and substances we so often hear about. With the genetic basis of cancer, it comes as no surprise that a good understanding of what’s happening on a genetic level can help scientists develop effective ways to combat these unwanted changes in our DNA.

Anticancer drug therapy, widely known as chemotherapy, uses medication to kill or slow down cancer cell growth. However, its effectiveness has huge fluctuations between individuals. The outcomes in some people are promising, while the same anticancer drug might have little to no effect in others with the same classification of tumor. The unpredictability of anticancer therapy outcomes is due to the diversity of genetic backgrounds of each patient. This is where precision oncology comes in. Defining a genetic characterization for individual tumors and how they will respond to anticancer drugs is key in guiding optimal patient tailored therapy on a case-by-case basis.

Image explaining pharmacogenetics concept

A recent study by Dr. Lee and his team of scientists in Seoul, South Korea has established innovative pharmacogenomic work where they genetically mapped out a panel of tumor cells derived from cancer patients and then determined how these will react to commonly used anticancer drugs. This ground-breaking research and others like it, are paving the way for the push towards precision cancer therapy. The researchers tested 462 different tumor cells of 14 different cancer types against a panel of 60 different drugs, giving us a large-scale landscape that can inform doctors on how each individual is going to respond to different medications, and what potential combination of treatments might work best, based on their genetic background.

Some of the key findings of the research was a specific mutation in the KRAS gene that resulted in pretty intense sensitivity to a specific group of drugs. Some of the most commonly used anticancer drugs that researchers found to be very sensitive to the KRAS mutation are the Novartis anti-breast breast drug Alpelisib and Trametinib, used to treat skin cancer. In addition, Dr. Lee and his team identified that alterations to the EGFR gene are highly linked to sensitivity of another drug called Ibrutinib, used to treat brain cancer patients.

When the team of scientists tested these sensitivities they observed in the lab on real tumors, they found that the top 30% most sensitive to any particular drug, had a partial or complete response with an average duration of 6 months.

The graph below is a comprehensive large-scale landscape of the findings that Dr. Lee and his team discovered. It maps out the different genetic markers identified and the sensitivities (blue lines) and resistance (red lines) they each provide to the large set of anti-cancer drugs that the researchers looked at. Essentially the graph depicts all the genomic associated drug interactions. On the periphery of that circle are all the different drug family types and inside are all the different biological markers they correspond to.

Image of cancer pharmacogenetic map

Click on the image above to go to website where you can explore cancer-drug interactions.

Advances like this one are making great strides in the field of oncology, showing us the potential for pharmacogenomic testing to improve treatment outcomes. The importance and need for individualized treatment is coming to the forefront, as we learn more about its effectiveness in treating cancer. As the research suggests, our DNA holds an important key to unlocking our optimal health. The future of cancer treatment is in precision medicine, where each individual will have the benefit of an anticancer therapy program tailored specifically for them.

 

This article has been produced by Diana Hernandez. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

 

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