Bioscience

Spate of cancer-research findings underscore state’s strength

April 22, 2008

By Flinn Foundation

Compiled from media reports

Arizona research teams have repeatedly made headlines in recent weeks, announcing significant advances toward better understanding of and treatments for several types of cancer. The findings illustrate the steady progress the scientific community is making toward cementing Arizona’s position as a leading center for cancer research.

Among the recently reported findings:

Existing drugs paired to prevent colon cancer

A new drug cocktail being studied by University of Arizona scientists appears to cut by 90 percent the chance that high-risk patients will develop colon cancer. UA scientists revealed the extraordinary results of a 300-person clinical trial April 14 at the annual meeting of the American Association for Cancer Research (AACR) in San Diego.

The study, led by Eugene Gerner, director of the Arizona Cancer Center‘s gastrointestinal cancer program, and University of California at Irvine researcher Frank Meyskens, formerly of UA, examined the combined application of the known cancer-fighting drug DFMO and the anti-inflammatory sulindac for patients who had developed pre-cancerous colon polyps.

After three years of receiving the therapy, the researchers found that patients’ risk of developing additional dangerous polyps fell 70 percent. For those who already had large or multiple polyps, the risk of recurrence plummeted 95 percent, an improvement more than twice what other preventative treatments have been able to show.

“It is by a long shot the most effective therapy we have found to prevent this cancer, with very little toxicity,” said David Alberts, director of the Arizona Cancer Center, in the Arizona Daily Star.

“Further testing will tell us if this therapy might be useful for others at risk — those who have a family history of colon cancer, but have not yet developed polyps,” Dr. Gerner said in the Daily Star.

DFMO, or difluoromethylornithine, is a synthetic amino acid known  to inhibit the rapid cell proliferation that occurs in cancerous tissue. Used alone at the dosage level necessary for an anti-carcinogenic effect, DFMO would be toxic, but combined with sulindac, its dosage can be dramatically reduced while maintaining efficacy.

Drugs for skin, pancreatic cancer show strong results in trials

A team of researchers from the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare have announced promising findings from clinical trials on two drug therapies, one for advanced basal-cell carcinoma, a type of skin cancer, the other for pancreatic cancer. The studies were led by Daniel Von Hoff, physician-in-chief at TGen and the chief medical officer for Scottsdale Healthcare. Like the UA group studying colon cancer, Dr. Von Hoff reported his team’s results during the AACR’s annual meeting.

Basal-cell carcinomas, the most common skin cancers, are typically identified long before they become dangerous, but can affect deeper tissue and bones if left untreated. Dr. Von Hoff reported that the drug candidate GDC-0499 shrank advanced basal-cell carcinomas in eight of the nine Phase-1 trial participants. The drug, developed by the biotech firm Genentech, was tested in Scottsdale, at Johns Hopkins University in Baltimore, and at the Karmanos Cancer Institute in Detroit.

“It has had a pretty dramatic effect,” Dr. Von Hoff said in the Arizona Republic. “I think this fulfills the promise of what targeted therapies can do, with dramatic effects and low side effects.”

The pancreatic-cancer Phase-1 trial examined the effect of combining two existing drugs, gemcitabine and nab-pacilitaxel. Tumors shrank in 60 percent of patients, Dr. Von Hoff said in the Republic.

The pancreatic-cancer trial was sponsored by Abraxis Bioscience, a Los Angeles-based firm that has recently expanded to Phoenix. Abraxis currently markets Nab-pacilitaxel as Abraxane for Injectable Suspension, which was approved by the Food and Drug Administration in 2005 for treatment of certain metastatic breast cancer patients.

Dr. Von Hoff’s group conducted the pancreatic-cancer study using a protein-based test developed by Abraxis and Caris MPI. (Caris MPI, known as the Molecular Profiling Institute until its January acquisition by Caris Ltd., was a spinoff of TGen and the International Genomics Consortium.)

Researchers design new model for progression of multiple myeloma

After six years of study, researchers at the Mayo Clinic in Scottsdale reported in the February issue of Cancer Cell that they have successfully designed a genetically engineered mouse model for the progression of multiple myeloma. The model, which demonstrates how a benign tumor can become malignant cancer, constitutes an important step toward understanding the genetic factors in development of multiple myeloma, the second most-common cancer of the blood.

Myeloma typically develops after formation of a blood plasma disorder called MGUS, or monoclonal gammopathy of undetermined significance. One to three percent of individuals over age 50 develop MGUS, and in a small percentage of cases, MGUS becomes malignant, causing myeloma’s characteristic proliferation of bone-marrow plasma cells, ultimately leading to osteoporosis and destruction of the bone marrow.

The Mayo scientists, led by Leif Bergsagel, proved through the mouse model that the transition to malignancy occurs in the presence of the cancer-causing gene MYC, long suspected to have a relationship to myeloma.

“Some aspects of the progression of myeloma are due to the acquisition of genetic mutations over time,” said Dr. Bergsagel. “With this model we can identify those mutations more quickly, and better understand what’s happening with the patient.

“We’ve proven that MYC can cause the conversion,” he added. “Now we can move forward and target new therapies to prevent that from happening.”

The recent findings in cancer research follow industry announcements of new options for breast-cancer detection and skin-cancer prevention:

UA-related firm announces successful trial for skin-cancer inhibitor

In March, Niadyne Inc., a skin-care products firm founded by University of Arizona professors Myron and Elaine Jacobson, announced that it had completed the first round of clinical trials for myristyl nicotinate (MN), a niacin-derived topical cream that acts on actinic keratoses, scaly skin lesions that can develop into skin cancers. The second round of trials on MN, which Niadyne is studying in partnership with the Arizona Cancer Center under a National Cancer Institute grant, should begin within the next few months.

“We’re really looking at the ability of myristyl nicotinate to prevent the formation of actinic keratoses,” said Myron Jacobson, in the Arizona Daily Star.

David Alberts, director of the Arizona Cancer Center, helped to design the clinical trials on MN. He said in the Daily Star that preclinical results indicate the drug restores rather than kills damaged cells.

Niadyne, which has its business headquarters in North Carolina and its research laboratories in Tucson, currently markets four other product lines that contain niacin derivatives. Among them is NIA 24, a niacin-based cream intended to repair sun-damaged skin and prevent further damage, which is sold through dermatologists’ and plastic surgeons’ offices and some medi-spas.

Diagnostics firm launches test for breast-cancer detection

In January, Phoenix-based Provista Life Sciences LLC, a diagnostic development and commercialization firm, announced that it was introducing to market its Biomarker Translation Test (BT Test), a blood test to be used initially in conjunction with a mammogram for early detection of breast cancer. In December, Provista had completed clinical trials on the test, which the firm suggested could more accurately diagnose breast cancer than could a mammogram alone, and do so more cheaply than other existing diagnostic tests.

Because the BT Test looks for molecular-level indications that breast cancer is present, Provista asserts that the diagnostic might enable diagnosis before a tumor grows large enough for physical detection. Provista explained in a white paper it authored that the BT Test is intended to assess up to five “known protein biomarkers associated with breast cancer and combine them with a patient’s unique personal chemistry and health profile to make a diagnosis.”

“Our goal is to encourage women to take action and get screened as soon as possible, as early detection provides the best chance for a cure,” said Dr. Louis Kirby, Provista’s chief medical officer, in the Business Journal of Phoenix.


For more information:

Cancer-drug trials show promise,” Arizona Republic, 04/16/2008

UA ‘home run’ is hit vs. cancer of colon,” Arizona Daily Star/EM>, 04/15/2008

Mayo Clinic cancer model to speed up drug research,” Arizona Republic, 04/17/2008

Mayo Clinic media release

Tucson firm seeks approval for new drug to avert skin cancer,” Arizona Daily Star, 03/14/2008

Blood test for breast cancer hits the market,” Business Journal of Phoenix, 01/29/2008