Early stage scientific activities essential for pioneering new approaches to cancer treatment and prevention are rarely eligible for federal funding. The grant approval process requires substantial proof-of-concept work before an application is considered competitive for funding. Private donations are essential for providing investigators with the opportunity to launch promising new pilot projects. Hutchinson Center faculty members are extremely successful in leveraging pilot funding to garner federal or foundation grants of 10 or even 100 times the initial investment.
Typically small in scale, pilot studies help researchers collect data quickly to test new hypotheses and refine methodologies. These are the projects at the leading edges of science, allowing scientists to explore novel ideas that stretch the boundaries of our understanding. Pilot studies can also jumpstart the careers of young investigators, contributing to their training and even helping them obtain faculty positions at the Center and other prestigious research institutions.
Below we highlight several such projects that have led to novel discoveries and larger studies funded by federal or foundation grants.
Exploring new treatment options for kidney cancer
Drs. Hootie Warren and Scott Tykodi of the Center's Clinical Research Division have found evidence that blood stem-cell transplantation, a key treatment for individuals with blood cancers, could be used to treat an advanced form of kidney cancer that is almost impossible to cure with existing therapies. Using $25,000 in pilot funds, the team discovered that certain proteins produced by solid tumors may provoke a cancer-fighting response from donor immune cells. Based on this early success, the National Cancer Institute funded two five-year grants totaling over $1.7 million to help Drs. Warren and Tykodi continue their work.
In addition to mounting an immune response against cancer cells, the donor immune cells, called T cells, may also attack a patient's healthy cells. This response produces an often severe transplant complication called graft-vs.-host disease. The researchers hope to identify the unique characteristics of the tumor cells (and not present on normal cells) that enable the donor-T cells to recognize only the cancer. Once found, the target proteins may be used to boost the transplant's cancer-fighting effect while reducing the graft-vs.-host response. These novel targets on tumors could also be used to develop vaccines that could stimulate a patient's own immune response after transplant.
Gaining cancer insights from studies on cell division and growth
Some of the most common problems in human cancers occur when the molecules responsible for regulating cell growth and division malfunction. Scientists know the pathways that govern cell growth and division are closely connected, but the exact nature of that connection has been difficult to determine. To better understand these processes, Dr. Bruce Edgar of the Center's Basic Science Division began a systematic search for genes that interact with two known regulators of cell growth. These experiments revealed a previously unknown role for the proteins in cell growth and laid the critical groundwork for additional studies to probe the relationship between cell growth, division and cancer.
Dr. Edgar used the results of the pilot study to obtain $1.3 million in federal funding to continue and extend this work. As they tease apart the molecular events that govern and link cell growth and division, scientists will gain a better understanding of the defects that give rise to cancer. This knowledge will help researchers design tools to improve cancer diagnosis and treatment.
Designing treatments for drug-resistant cancer cells
When something goes seriously wrong in a cell, such as irreparable DNA damage, the cell usually self-destructs. This process is controlled in part by a family of proteins, some of which are responsible for promoting cell death and others — including one called Bcl-xL — for keeping cells alive. Bcl-xL is overabundant in many kinds of cancer cells, including myeloma cells and liver and colon tumor cells, which makes them resistant to traditional chemotherapies and, consequently, hard to kill. However, a pilot study led by Dr. David Hockenbery of the Center's Clinical Research Division demonstrated that a commonly used laboratory chemical called antimycin A (AA) can kill cells by binding to and blocking the function of Bcl-xL.
Because AA can also have negative effects on healthy cells, it is not a good candidate for cancer therapy. Instead, researchers will use what they learn about the interactions between AA and Bcl-xL to build similar molecules that can kill cancer cells without harming healthy cells. Results from Dr. Hockenbery's $20,000 pilot study led to three other grants totaling more than $2 million that allowed the researchers to investigate how AA promotes cell death. Understanding these details lays the groundwork for developing anti-cancer drugs that can destroy drug-resistant tumors with fewer side effects.
