Cancer Research Collaboration of Excellence in Tumor Microenvironment Studies

The Cancer Research Collaboration of Excellence (CRCE) in Tumor Microenvironment Studies, established in May 2021, is a multidisciplinary team of researchers in five departments at Kansas State University investigating the tumor microenvironment to improve cancer therapeutics.

Many conventional cancer therapies fail due to factors related to the tumor's environment, called the microenvironment. This CRCE, led by Brad Behnke, professor of kinesiology, is examining the tumor microenvironment from many angles. Members are investigating the initiation of DNA mutations caused by low-dose radiation, the tumor blood vessel network and oxygenation, and vitamin D's relationship to cancer.

The collaboration members are independently, yet synergistically, conducting four projects aimed at understanding and combatting the tumor microenvironment and improving cancer therapies.

Questions this research aims to answer:

1. What DNA mutations occur in response to radiation?
2. Does exercise increase oxygenation in breast tumors (which are resistant to chemotherapy and radiation in the absence of oxygen)?
3. Does nitrate supplementation increase tumor oxygenation and decrease tumor growth?
4. What are the vitamin D needs of ovarian tumors (considering that vitamin D status seems to relate to tumor progression)?

Project 1 - Low-Level Radiation Exposure Cancer Research

This project aims at better understanding the DNA mutations caused by radiation and the subsequent development of cancer. Investigators will use radiobiology to examine the biological mechanisms and processes involved in DNA mutations caused by low-level radiation exposure. Low-level radiation exposure occurs in radiation workers, medical patients undergoing radiotherapy, victims of accidental or intentional release of radioactive material, and NASA astronauts. The researchers ultimately aim to develop therapeutics to stop the DNA mutations and reduce the public health burden associated with radiation-caused cancer.

Project 2 - Manipulation of tumor oxygenation with exercise to enhance radiation damage in a novel intraductal breast cancer model

This project aims at determining the effects of aerobic exercise therapy (AET) on breast cancer tumor responses to radiation. These therapies are commonly used by cancer patients to improve quality of life. Solid tumors contain regions of hypoxic (low oxygen level/pressure) cells known to be resistant to radiation therapy. AET may improve tumor perfusion (blood circulation) and reduce tumor hypoxia. Patients who do aerobic exercise after cancer diagnosis demonstrate improved survivorship. This may be because it both makes tumors more susceptible to anti-cancer therapy and protects healthy tissue from radiation (and chemotherapy) damage. This project aims to determine the molecular mechanisms by which AET affects radiation response in breast tumors.

Project 3 - Effects of dietary nitrate supplementation and soluble guanylyl cyclase activation/stimulation on tumor oxygenation and microcirculation

Hypoxia (low oxygen pressure/level) can make tumors resistant to radiation treatment. Strategies that may improve tumor oxygenation, such as elevating nitric oxide bioavailability and treating with antioxidants, may slow or prevent tumor growth. Dietary supplementation with beetroot juice, a concentrated source of nitrate and nitrite, has many positive effects, including increasing blood flow to some tissues and improving energy production by increasing mitochondrial efficiency and reducing metabolic demands. This project will investigate whether this process occurs in tumors at sufficient levels to raise oxygen pressures and reduce or prevent hypoxic oscillations, thus slowing tumor growth and improving radiotherapeutics.

Project 4 - Vitamin D receptor polymorphisms and microRNA expression in ovarian cancer

This project will determine if circulating vitamin D modifies the tumor microenvironment, and if so, how this occurs. This information will be used to predict treatment complications, completion and overall survival in ovarian cancer. Earlier work from this group demonstrated that low serum vitamin D status before treatment is associated with increased tumor size and lower survival rates. This project aims to extend our knowledge of the role of vitamin D status in mediating postsurgical outcomes in a larger, more diverse, cohort of women, and to elucidate the molecular steps in the vitamin D signaling pathway.

Investigators:

Brad Behnke, Kinesiology, Principal Investigator

Amir Bahadori, Mechanical & Nuclear Engineering

Carl Ade, Kinesiology

David Poole, Anatomy & Physiology and Kinesiology

Chieko Azuma, Radiation Oncology

Wei-Wen Hsu, Statistics