Research conducted by the Phoenix Children's Research Institute at the University of Arizona College of Medicine – Phoenix shows normalizing cancer tumor vessels and alleviating low oxygen levels in the tumor microenvironment can improve the effectiveness of chemotherapy treatment in lung cancer, according to a paper published in EMBO Molecular Medicine.
The study, “FOXF1 promotes tumor vessel normalization and prevents lung cancer progression through FZD4,” which was co-authored by Tanya Kalin, MD, PhD, is a complete pivot from how researchers have historically studied cancer treatment by providing a solution that strengthens blood vessels feeding cancer tumors.
“Cancer research is often focused on ways to deplete cancer tumors of blood vessels and oxygen by basically starving the cancer cells to prevent tumor growth and metastasis, but it was shown this approach can make the tumor cells become even more aggressive and metastatic,” said Dr. Kalin, who is vice chair of translational research for the Phoenix Children's Center for Cancer and Blood Disorders and professor of child health at the University of Arizona College of Medicine – Phoenix. “Our study takes a completely different approach and instead of obliterating the tumor-associated blood vessels, we normalize and repair the tumor vessels by increasing the FOXF1 protein in endothelial cells, which, in turn, prevents lung cancer progression.”
Dr. Kalin, whose work focuses on developing effective treatments for pediatric cancers, has spent the last few decades researching how to create a non-toxic small molecule inhibitor compound to kill cancer cells and developing tumor-cell-specific nanoparticles that deliver the inhibitor compound directly to cancer cells, blocking specific targeted proteins.
This lung cancer study builds upon her years of scientific research to create a more targeted approach to cancer treatment. The insertion of the FOXF1 protein increases tumor vessel stability and stimulates nanoparticle delivery into the cancer-causing cells, which destroys them from the inside with minimal chemotherapy.
“This is a promising study for future therapies in non-small cell lung cancer and other types of cancer and will hopefully change how we look at cancer treatment moving forward,” said Dr. Kalin.
Lung cancer is the leading cause of cancer-related mortality worldwide. Current treatment strategies include chemotherapy and/or radiotherapy, and surgery in the case of patients diagnosed with early-stage lung cancer. The five-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) remains less than 20%, emphasizing a need to develop better treatment strategies. Interactions between the tumor-microenvironment and tumor cells play a crucial role in tumor progression and, to date, traditional therapies have failed to improve overall survival of lung cancer patients, suggesting a deeper understanding of tumor-associated vascular biology is required.
“Every breakthrough in pediatric cancer research is cause for celebration, especially studies like Dr. Kalin's that shed light on tumor microenvironments and stopping the spread of cancer,” said Stewart Goldman, MD, senior vice president of research for Phoenix Children's, and Sybil B. Harrington, endowed chair and professor of child health at University of Arizona College of Medicine – Phoenix. “Dr. Kalin's remarkable findings will have implications for non-small cell lung cancer, as well as many childhood cancers, hopefully changing cancer therapies in the near term, and I believe this research will be one of the most cited cancer research studies for years to come.”
In March, Phoenix Children's released another study, “CRISPR/Cas9 Genome Editing Allows Generation of the Mouse Lung in a Rat,” that focuses on finding an innovative solution for babies born with chronic lung diseases caused by either prematurity or severe genetic conditions.
