Study Looks Into Mutations That Cause Resistance to Cancer Therapies

August 25, 2021 11:34:31

A study conducted by researchers from UT Southwestern has discovered that mutating genes to create proteins that drive cancer using a virus may allow scientists to better understand the resistance that develops to the cancer treatments used to target them. The researchers’ findings were published in “Cancer Research,” with the scientists noting that their discovery could assist in better understanding the interaction between treatments and their target proteins, as well as in the development of treatments that bypass resistance.

Dr. Ralf Kittler from the Eugene McDermott Center for Human Growth and Development, who is the research leader, stated that the researchers’ approach could be a handy tool in the fight against therapeutic resistance in cancer and had the potential to be useful in other areas of drug development as well. The associate professor of pharmacology co-led the research with Professor John Minna, who is also the director of the Hamon Center for Therapeutic Oncology Research.

Targeted therapies are made up of drugs that alter the function of specific proteins which drive tumor growth and spread. They are often administered orally and not only prolong survival but also offer symptom relief. However, Kittler stated that targeted therapies lose their efficacy over time as tumors grow more resistant when the genes mutate and produce proteins that don’t bind with the therapies.

For instance, he explained, patients suffering from non-small cell lung cancer were usually treated with therapies that inhibit the epidermal growth factor receptor protein. Sadly, a majority of these tumors become resistant to the therapy in a year. This has prompted researchers to create different versions of drugs that target epidermal growth factor receptor proteins in an attempt to overcome this resistance.

For their study, the researchers created LentiMutate, which they used to better predict drug resistance. Their approach is based on viruses known as lentiviruses, which cause mutations. This class of viruses infects its target cells to produce proteins and also converts RNA to DNA. However, this process is prone to error, which is why the researchers utilized the vector to introduce epidermal growth factor receptor RNA in human cells, which caused the cells to create mutant versions of this protein.

The researchers then introduced an inhibitor known as gefitinib to the cells to search for the resistant cells. This allowed then to identify mutations that triggered the protein resistance to gefitinib. They also identified mutations that cause resistance to the drugs that target the proteins which drive non-small cell lung cancer and chronic myelogenous leukemia. Kittler asserted that using LentiMutate to identify these mutations could help develop new drugs that bind to therapy-resistant mutant proteins.

As cancer treatment takes this route of targeting mutant genes, it is likely that diagnosis and treatment will reach a personalized level in the way that companies such as Predictive Oncology (NASDAQ: POAI) have been working to make possible.

NOTE TO INVESTORS: The latest news and updates relating to Predictive Oncology (NASDAQ: POAI) are available in the company’s newsroom at

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