Project Zero Delay Speeds Drug to Patients in Record Time
A Phase I clinical trial enrolled its first patient only two days after U.S. Food and Drug Administration clearance of the experimental drug for a first-in-human cancer trial, a milestone that normally takes three to six months. Investigators from MD Anderson and pharmaceutical company AstraZeneca reported their work in the Journal of Clinical Oncology published online in August.
The joint effort, dubbed Project Zero Delay, is part of a strategic collaboration between the two organizations designed to safely accelerate development of new cancer drugs. In many cases that process takes about 12 years, and the cost of bringing a new drug to patients has been
estimated at around $1.3 billion.
“Project Zero Delay demonstrates how we can shrink the time it takes to bring new drugs to cancer patients,” says Robert C. Bast Jr., M.D., vice president for translational research at MD Anderson and the paper’s senior author. “Close cooperation eliminated unnecessary delays while fully meeting regulatory requirements for scientific and human safety review.”
The key to Project Zero Delay was performing most tasks in parallel instead of sequentially, says lead author Razelle Kurzrock, M.D., professor and chair of the Department of Investigational Therapeutics. No administrative steps were skipped.
Study Uncovers Genetic Link for Bladder Cancer
A research team led by MD Anderson has pinpointed a gene variation, prostate stem cell antigen, or PSCA , that causes a 30 percent to 40 percent higher risk for urinary bladder cancer. Scientists hope the results of this international study may help determine who is at high risk to contract this deadly cancer. They also hope the knowledge may improve survival rates and result in chemopreventive interventions.
PSCA is overexpressed in prostate cancer, and the level of PSCA increases with tumor grade and stage. While PSCA ’s involvement in bladder cancer had been suggested previously, this is the first time it has been linked definitively.
The study answers many questions about genetic causes of bladder cancer, says Xifeng Wu, M.D., Ph.D., professor in epidemiology and the lead and corresponding author.
“The neighboring genomic region has previously been identified as a possible problem for breast, prostate, colorectal and bladder cancer, but we didn’t know why,” says Wu, who hopes the group’s findings will help targeted bladder cancer prevention efforts.
This study was supported by grants from the National Cancer Institute and funding from MD Anderson’s Kleberg Center for Molecular Markers.
Delivering Chemotherapy Straight to Ovarian Cancer Cells
A research team led by scientists at MD Anderson has used a novel carrier system using the EphA2 protein as a homing mechanism to deliver chemotherapy directly to ovarian cancer cells in preclinical models.
EphA2 has increased expression in ovarian and other cancers, including breast, colon, prostate and non-small cell lung cancers and aggressive melanomas. Its expression has been associated with poor prognosis.
“One of our goals has been to develop more specific ways to deliver chemotherapeutic drugs,” says senior author Anil K. Sood, M.D., professor gynecologic oncology and cancer biology. “EphA2’s preferential presence on tumor cells makes it an attractive therapeutic target.”
Sood, co-director of the Center for RNA Interference and Non-Coding RNA and the Blanton-Davis Ovarian Cancer Research Program at MD Anderson, says the drug was highly effective in reducing tumor growth and in prolonging survival in preclinical animal models. Researchers are “gearing up” to bring EphA2-silencing therapy to Phase I clinical trials, he adds.
Research was funded by a National Cancer Institute-United States Department of Health and Human Services-National Institutes of Health T32 Training Grant. Additional support came from MD Anderson’s ovarian cancer Specialized Program of Research Excellence grant, the Marcus Foundation, the Gynecologic Cancer Foundation, the Entertainment Industry Foundation, the Blanton-Davis Ovarian Cancer Research Program and Sood’s Betty Ann Asche Murray Distinguished Professorship.
Common Diabetes Drug Reduces Pancreatic Cancer Risk
By taking metformin, the most commonly prescribed anti-diabetic drug, people can reduce the risk of developing pancreatic cancer by 62 percent, according to MD Anderson researchers.
“This is the first epidemiological study of metformin in the cancer population, and it offers an exciting direction for future chemoprevention research for a disease greatly in need of
treatment and prevention strategies,” says Donghui Li, Ph.D., professor of gastrointestinal medical oncology.
According to Li, the study’s senior author, more than 35 million prescriptions for the oral medication are filled annually. It’s most often given to type 2 diabetes patients who are obese and/or have insulin resistance.
Li cites a previous animal study showing that metformin prevented pancreatic tumor development, as well as numerous epidemiologic studies in diabetics showing the drug reduced the risk for cancer overall.
“Given these earlier findings, and knowing that diabetes is a risk factor for developing pancreatic cancer and that 10 percent of such cancers are associated with diabetes, we wanted to better understand the specific association between antidiabetic therapies and this lethal disease,” says Li.
The study was supported by the National Cancer Institute, as well as by institutional funds.
Protein Dubbed ‘Swiss Army Knife’ of DNA Repair
A protein specialist that opens the genomic door for DNA repair and gene expression also turns out to be a multitasking workhorse that protects the tips of chromosomes and dabbles in a protein-destruction complex, reports a team led by researchers at MD Anderson.
“Instead of being a really important tool dedicated just to regulation of gene transcription, Gcn5 is more like a Swiss Army knife that performs different functions depending on what needs to be done in the cell,” says senior author Sharon Dent, Ph.D., professor of biochemistry and
molecular biology.
The researchers document a chain of events that starts with depletion of Gcn5, which leads to decreased activity by another protein that protects yet a third protein from destruction. That last protein, TRF 1, protects telomeres, dense structures at the ends of chromosomes that, like the compressed plastic tips on the ends of a shoelace, keep the chromosome ends intact.
Variation in the gene that expresses the middle protein in this model is part of an 11-gene signature associated with highly metastatic cancers and poor prognosis, the authors note.
Funding for the study came from the National Institutes of Health and the French National Research Agency and the Fondation pour la Recherche Médicale in France.
