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Providence researchers help identify drug resistance and reversal mechanisms in breast cancer

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  • Drug resistance is a major challenge faced today by cancer patients, researchers, and caregivers.
  • Three new publications co-authored by experts from the Providence Research Network show how identifiable mechanisms in a tumor can help predict a patient’s response to cancer therapies, as well as potential approaches to reversing drug resistance.

Drug resistance is one of the major challenges faced today by cancer patients, researchers, and caregivers. While many treatments exist and promising new drugs continue to emerge, it can be difficult to evaluate whether a patient’s tumors will respond to or develop immune responses to specific therapies. Historically, that has limited the options available to patients, especially those with later stage cancers such as advanced breast cancer.

But what if it were possible to identify the factors that cause drug resistance in the first place and use that information to shape more effective therapies – or even to reverse that resistance?

That question is at the heart of a recently published body of research from several global teams of cancer scientists, including Professor Dave S.B. Hoon, Ph.D., and Assistant Professor Matias Bustos, Ph.D., of the Providence Saint John’s Cancer Institute Department of Translational Molecular Medicine. In collaboration with global partners including Qiang Yu, MD, Ph.D., of the Genome Institute of Singapore (GIS), Yosef Shiloh, Ph.D., at Tel-Aviv University, and Peter Bostick, MD, at Baton Rouge General Medical Center, they’ve co-authored three studies focused on identifying the factors behind drug resistance, and those factors' impacts on therapies currently available for breast cancer.

The research was recently published in three influential peer-reviewed journals: Proceedings of the National Academy of Sciences USA (PNAS), Clinical and Translational Medicine, and Nature Communications.

Overall, their findings showed how identifiable mechanisms in a tumor can help predict a patient’s response to cancer therapies, as well as potential approaches to reversing drug resistance.

Dr. Dave HoonAccording to Dr. Hoon, this has real-world implications both now and in the not-too-distant future: “If you can identify drug resistant factors within a patient’s tumor, you’re in a much better position to evaluate which therapies will work for that patient prior to treatment. That’s extremely valuable information for providers, patients, and families who want to ensure the patient receives the most effective treatment possible.”

He also points to an emerging generation of “epigenetic” therapies anticipated to become more available in clinical settings. These are medications that influence cancer cell behavior, altering the expression of genes without altering the DNA code. Dr. Hoon adds that “as new epigenetic medications continue to move through human trials, we’ll have even more tools available in the clinic to better target treatments and reverse drug resistance.”  

In their recent studies, the researchers demonstrated that epigenetic modification of breast tumor cells allowed them to reactivate suppressed immune responses to kill the tumor cells. It is known how medications like Cisplatin (Platinol®), a DNA damage drug, eventually can lead to drug resistance in a very aggressive form of breast cancer (triple negative). One of the studies, published in Clinical and Translational Medicine, identified a protein that results in this drug resistance and can be predictive of Cisplatin resistance.

For Dr. Hoon, these findings and ongoing progress in the field of precision cancer care boil down to one important takeaway: more hope for those with advanced cancers and all who care for them. The group continues identifying new epigenetic targets that influence drug resistance in breast cancer and other cancers. 

Read the research publications at the links below:

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