New answers for cancer

The Feist-Weiller Cancer Center in Shreveport is bringing research, education, and treatment together.

You. Have. Cancer. Time stands still for just a moment when those three little words are spoken, but then they become a call to action. No longer a question of "why," the "where" and "who" take over. Where do I go for help? Who will help me fight the cancer?

The newly opened Feist-Weiller Cancer Center at Louisiana State University Health Sciences Center in Shreveport is the answer to the "where" question for thousands of new patients from Shreveport and the surrounding Ark-La-Tex area each year. Meanwhile, the discoveries made at an academic medical center such as Feist-Weiller make it easier to know "who" can help fight the disease as well.

While the Feist-Weiller Cancer Center is equipped for state-of-the-art diagnostics and treatment in a beautiful building decorated with artwork created by cancer patients themselves, it goes far beyond bricks and boards. The Feist-Weiller Cancer Center is founded on three principles: research, education, and treatment.

The hallmark of the Feist-Weiller Cancer Center is a multidisciplinary approach between and among physicians and scientists with the goal of bringing the latest in cancer research and treatment to the community. At the same time, the center has a mission of educating future physicians and scientists, as well as the local community, in order to reduce cancer risk and mortality.

One of the ways that the Feist-Weiller Cancer Center brings research and treatment together is through the interactions between members of the Translation Control Group. This group of nine clinicians and basic scientists is one of the four scientific programs within the Feist-Weiller Cancer Center. Their mission, according to the group's leader, associate professor of urology Jill Williams, Ph.D., is to bring what scientists refer to as "translation modifiers" to clinical use. This function also illustrates one of the basic goals at Feist-Weiller: meshing the work of basic scientists with clinicians, bringing what lab researchers discover from the benchtop to the bedside.

But how does the group's work "translate" to the world of science, cells, and molecules? They work at the least studied end of genetics, which is characterized by a continuum of synthesis from DNA to RNA to protein. Simply put, the group wants to know how the machinery that "translates" a programmed genetic pathway into proteins can go awry and transform a normal cell into a cancer cell. Though the translation process is fundamental to the way cells work, using it to understand cancer is a novel and understudied concept that has only recently moved to the forefront of cancer research.

According to Williams, since the Translation Control Program was organized three years ago, a review of professional literature shows that the group has emerged as the national leader in the field of translation involvement in cancer-particularly its application to cancer diagnosis and treatment.

The collaboration between basic scientists and clinicians has borne fruit recently with the funding of a $1.1 million dollar grant from the National Institutes of Health to Dr. Cherie-Ann Nathan, another member of the Translation Control Group and a noted professor of otolaryngology at LSUHSC-S. Nathan's specialty is head and neck cancer, and her grant centers on clinical applications of some basic principles of translation control of cancer progression.

"The grant will allow us to test our hypothesis in a multi-institutional trial and, more importantly, determine whether patients will benefit," Nathan says.

Benefiting patients is the goal of both the clinicians and basic scientists in the Feist-Weiller Cancer Center. One of the proteins that regulates the first steps in translation, eIF4E, drives many aspects of tumor progression, but it also may help predict which patients will quickly have recurrent tumors. Identifying which patients are most likely to recur allows the physician to aggressively treat them with chemotherapy, radiation and other therapies in addition to surgery.

In the past, clinicians have had to rely on diagnosis and prognosis based on the physical characteristics of cells in a biopsy or tumor tissue-tumor cells have a different "look" from normal cells. Use of eIF4E as a cancer protein that appears in cells before they look like tumor cells brings cancer prognosis to the molecular age.

After surgery, "Did you get it all?" is a common question asked by cancer patients and their families. Now, Nathan has a better idea of whether there is a positive margin at the molecular level and whether or not the cancer cells are coming back. Not only can a pathologist check for cellular changes, but Nathan can look for the presence of eIF4E to guide her patient care.

Nathan's NIH grant will not only support a multi-institutional trial with Johns Hopkins University to confirm the prognostic value of eIF4E, but will also evaluate what researchers call an "mTOR inhibitor" as an "adjuvant" therapy in treating head and neck cancers. mTOR is another protein in the translation pathway that may control how much eIF4E is present-and may, therefore, be a great target for new chemotherapeutics.

In the adjuvant trial, Nathan is testing an analogue of Rapamycin, already an approved medication, as a therapy that targets eIF4E and will help control cancer progression and recurrence. Such studies are possible at the Shreveport facility because Feist-Weiller has established the infrastructure needed to develop large clinical trials of "in-house" ideas and products.

Meanwhile, other members of the group are working to develop therapeutics based on either genetically lowering eIF4E levels or targeting other components in the pathway. Their approaches include both gene therapies and searching for drug-like compounds that will inhibit the machinery and have therapeutic benefit in clinical application.