News | Radiation Oncology | November 23, 2015

Targeting Newly Discovered Pathway Sensitizes Tumors to Radiation and Chemotherapy

In some patients, aggressive cancers can become resistant to chemotherapy and radiation treatments

In a paper published in the journal Nature Communications, University of California, San Diego School of Medicine researchers identified a pathway that causes the resistance and a new therapeutic drug that targets this pathway.

“It was previously known that RAF (a family of proteins that regulate cellular signaling) governs resistance to therapies. We discovered an undescribed role for RAF and learned precisely how it occurs in a broad range of cancers,” said lead author Sunil Advani, M.D., assistant professor in the Department of Radiation Medicine and Applied Sciences.

The pathway is used by tumor cells to protect DNA from damage. By inhibiting the pathway using a drug-like compound called KG5, researchers were able to reverse the resistance of tumors to both radiotherapy and certain classes of chemotherapies that induce genotoxic stress. The hope is to increase survival rates among patients with highly aggressive cancers, said Advani.

“We are taking the tumor’s defenses away by targeting this pathway. By developing this drug, we have the potential to enhance radiation sensitivity of cancer while sparing healthy tissue. This drug increases the DNA-damaging effects of radiation and certain chemotherapies,” said principal investigator David Cheresh, Ph.D., distinguished professor of pathology and associate director for Innovation and Industry Alliances at Moores Cancer Center at UC San Diego Health. “We essentially get more anti-tumor activity with less radiation or chemotherapeutic drug. This allows us to see the anti-tumor effect while reducing terrible side effects. We have seen this in pancreatic, brain and lung cancer cells both in cell culture and in tumors growing in mice.”

Radiation is the therapy of choice for certain cancers. In follow-up studies, researchers hope to enhance the design of KG5 to further improve its radio-sensitizing activity and safety profile so that it can be tested in patients.

“For patients with aggressive cancers, there may be no good options left,” said Advani. “Armed with this new approach, our goal is utilize such a drug to improve the clinical outcomes of some of the most widely used anti-cancer therapies.”

Co-authors of this study also include Maria Fernanda Camargo, Laetitia Seguin, Ainhoa Mielgo, Sudarshan Anand, Angel M. Hicks, Joseph Aguilera, Aleksandra Franovic, and Sara M. Weis of UC San Diego.

For more information: www.nature.com/ncomms/index.html

Related Content

RSNA Study Shows Real-Time Indicator Improves Mammographic Compression
News | Mammography | December 12, 2018
Sigmascreening recently announced that more than 100,000 women have had mammography exams with the Sensitive Sigma...
RaySearch Developing RayCommand Treatment Control System for U.K. Proton Therapy Facility
Technology | Radiation Therapy | December 10, 2018
RaySearch has decided to develop a treatment control system, RayCommand, to act as a link between its RayStation...
Youth Football Changes Nerve Fibers in Brain

Statistically significant clusters (red-colored) showing group differences (Control vs. Football) in white matter strain along the primary (F1) and secondary (F2) fibers. While body of corpus callosum (BBC) showed relative shrinkage in Football group, the other clusters showed relative stretching of fibers. PCR: Posterior Corona Radiata, PLIC: Posterior Limb of Internal Capsule, SCR: Superior Corona Radiata, SLF: Superior Longitudinal Fasciculus, SCC: Splenium of Corpus Callosum. Image courtesy of Kim et al.

News | Neuro Imaging | December 07, 2018
Magnetic resonance imaging (MRI) scans show repetitive blows to the head result in brain changes among youth football...
Mirada Medical Joins U.K. Consortium Exploring Healthcare AI
News | Artificial Intelligence | December 04, 2018
Mirada Medical, a leading global brand in medical imaging software, will form part of an artificial intelligence (AI)...
Sponsored Content | Videos | Radiation Oncology | November 30, 2018
Accuray's philosophy is to personalize treatments to exactly fit the patient.
Snoring Poses Greater Cardiac Risk to Women
News | Women's Health | November 29, 2018
Obstructive sleep apnea (OSA) and snoring may lead to earlier impairment of cardiac function in women than in men,...
Artificial Intelligence May Help Reduce Gadolinium Dose in MRI

Example of full-dose, 10 percent low-dose and algorithm-enhanced low-dose. Image courtesy of Enhao Gong, Ph.D.

News | Contrast Media | November 27, 2018
Researchers are using artificial intelligence (AI) to reduce the dose of a contrast agent that may be left behind in...
Women Benefit From Mammography Screening Beyond Age 75
News | Mammography | November 26, 2018
Women age 75 years and older should continue to get screening mammograms because of the comparatively high incidence of...
Ohio State University to Open Region’s First Proton Therapy Facility

Image courtesy of The Ohio State University James Comprehensive Cancer Center

News | Proton Therapy | November 21, 2018
The Ohio State University Wexner Medical Center and the Arthur G. James Cancer Hospital and Richard J. Solove Research...