Mayo Clinic researchers have developed a new proton therapy technique to specifically target cancer cells that are resistant to other treatments. This method is called LEAP, an acronym for “biologically enhanced biological therapy.” The results are published today in Cancer research, journal of the American Society for the Study of Cancer.
The human body receives tens of thousands of DNA diseases every day from a variety of internal and external sources. Thus, cells have developed complex repair pathways to effectively repair damaged DNA. Deficiencies in these repair pathways can lead to the development of diseases, including cancer, says Dr. Mutter. “
Robert Mutter, MD, Associate Chief Investigator and Radiation Oncologist, Mayo Clinic
“Deficiencies in the ATM-BRCA1-BRCA2 DNA repair pathway are often seen in cancer,” says Dr. Mutter. “And breast mutations and ovarian cancer mutations in BRCA1 and BRCA2 repair genes are the most common cause.”
Dr. Mutter; Zhenkun Lou, Ph.D., co-lead investigator of the study; and their colleagues studied an innovative way to deliver proton therapy to target tumors with sexually deficient pathways in the ATM-BRCA1-BRCA2 DNA repair pathway.
“We compared the effects of delivering the same amount of energy or dose into cancer cells using a dense energy deposition pattern with LEAP versus emitting the same more diffuse energy, which is normal for a photon. routine and proton therapy, ”says Dr Mutter. “Surprisingly, we found that cancers with sexual defects in the ATM-BRCA1-BRCA2 pathway are highly sensitive to a new proton-thickening mechanism.”
Dr. Lou says that the surrounding normal turf was saved, and that the fullness of DNA repair elements was still intact. “We also found that we were able to transform the DNA repair devices into pharmaceuticals by co-administering an ATM inhibitor, the body’s response regulator to DNA damage, to repair cells that are capable of repair make LEAP aware, “said Dr Lou.
Dr. Mutter states that the unique physical properties of protons allow oncologists to eradicate nearby conventional material with better precision, compared to conventional photon-based radiation therapy. “LEAP is a paradigm shift in treatment, where newly discovered biological responses could be introduced when proton energy deposition in cancer cells using novel radiation design techniques , enabling the personalization of radiotherapy based on patient tumor biology, “says Dr. Mutter.
Drs. Mutter and Lou say their findings are the result of several years of preclinical development through collaboration with experts in physics, radiation biology and DNA repair techniques. Dr. Mutter and the radiation oncology team at the Mayo Clinic are developing clinical trials to test the safety and efficacy of LEAP in several tumor types.