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New Proton Therapy Targets Treatment-Resistant Cancer Cells

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Researchers at the Mayo Clinic have developed a new proton therapy technique that more specifically targets cancer cells that resist other treatments. This technology is called LEAP and is an acronym for “biologically enhanced particle beam therapy.” The survey results are today Cancer research, Journal of the American Association for Cancer Research.

The human body suffers tens of thousands of DNA damages per day from a variety of internal and external sources. Therefore, cells have evolved complex repair pathways to efficiently repair damaged DNA. Deficiencies in these repair pathways can lead to the development of diseases, including cancer, Dr. Mutter said.

Mayo Clinic, Principal Investigator and Radiation Oncologist, MD, Robert Mutter

“Defects in the ATM-BRCA1-BRCA2 DNA repair pathway are commonly observed in cancer,” says Dr. Mutter. “And mutations in the BRCA1 and BRCA2 repair genes for breast and ovarian cancer are the most common causes.”

Dr. Mutter; Zhenkun Lou, Ph.D. , Co-principal Investigators of the Study; Their colleagues have researched new ways to provide proton therapy targeting tumors that have defects specific to the ATM-BRCA1-BRCA2 DNA repair pathway.

“Using a high-density energy storage pattern using LEAP, the effect of delivering the same amount of energy or dose to cancer cells and the same energy typical of conventional photon and proton therapy are more diffused and diffused. We compared the effects, “says Dr. Mutter. “Surprisingly, we found that cancers with defects specific to the ATM-BRCA1-BRCA2 pathway are very sensitive to new enriched proton technology.”

Dr. Lou says the surrounding normal tissue was spared and the complete complement of DNA repair elements remained intact. “Also, co-administration of ATM inhibitors, which are regulators of the body’s response to DNA damage, pharmacologically rewires the DNA repair mechanism and makes repair-capable cells highly sensitive to LEAP. I also found that I could do it, “says Dr. Lou.

Dr. Mutter states that the distinct physical properties of protons allow radiation oncologists to save nearby normal tissue with greater accuracy than traditional photon-based radiation therapy. “LEAP is a therapeutic paradigm shift based on the patient’s tumor biology with newly discovered biological responses triggered when proton energy deposits concentrate on cancer cells using new radiation planning techniques. It may be possible to personalize radiation therapy, “says Dr. Mutter.

Dr. Mutter and Lou state that their findings are the result of years of preclinical development in collaboration with experts in physics, radiobiology, and DNA repair mechanisms. Dr. Mutter and the Radiation Oncology team at the Mayo Clinic are developing clinical trials to test safety. Effectiveness of LEAP for multiple tumor types.

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