New anti-tumor compounds show such promise for fighting drug-resistant tumors that the National Institutes of Health (NIH) has placed them on the fast track for development.
The NIH awarded $1.35 million to Dr. Aleem Gangjee, Distinguished Professor of Medicinal Pharmacy at Duquesne University’s Mylan School of Pharmacy, to further develop compounds that fight against breast cancer that becomes resistant to Taxol and other drugs, as well as other drug-resistant types of cancer.
The five-year grant, awarded by the NIH’s National Cancer Institute (NCI), is the first given in this particular area to Gangjee, an international expert in folate, the vitamin that helps to produce new cells.
The NCI checks hundreds of promising compounds by running them through batteries of tests. Those showing the greatest potential are put on a fast track; Gangjee has three different compounds in this category.
Two of these compounds inhibit tumors by more than one method, with multiple-acting agents in a single drug. These innovative compounds are highly effective in circumventing problems typically associated with cancer treatments, including drug resistance that plagues current cancer medications.
Though many tests are yet to be done, the compounds are slated to begin the next step in animal studies with partners at the Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio, a patient care, research, prevention center that has achieved the NCI’s comprehensive cancer center rating. If the compounds continue to perform well in shrinking tumors without being toxic to other cells, they could move into human trials.
The water soluble compounds, Gangjee said, are easy to make and are shown to inhibit tumor cells at very low concentrations, factors that would help in administering a drug. Tests show the agents to be very effective at tricking the cancer cells into accepting them as one of the building blocks used to feed tumors.
Gangjee, who holds five concurrent NIH grants for cancer research, has developed many new compounds and received more than 25 patents in his 20 years of research at Duquesne. Recently, he became Duquesne’s first faculty member to have three patents issued within one month, including the fast-tracked compounds as well as compounds geared toward ovarian cancer. Their ovarian cancer-fighters work on the use of a selective transport system expressed by most types of this cancer, as well as 30 to 40 percent of breast, lung and kidney cancers. Ovarian, lung and pancreatic cancers are difficult to detect until later stages—and this drug works particularly well in late-stage cancer treatment, unlike many current cancer therapies.
These compounds target receptors expressed by tumor cells—typically not produced by normal cells. This distinction provides selectivity on where the drugs have impact, so they work as effective cancer treatment without any major toxicity to normal cells.
“One of the limitations of current cancer treatment is drug toxicity; it necessitates discontinuation of the drug, even if it is effective,” Gangjee said. “Because our compounds in this patent do not sicken patients and normal cells, it would not need to be discontinued.”
During the past 40 years, Gangjee’s cancer research has sprung from the inspiration of his family’s own experience with this stealthy disease. When Gangjee was 20 years old, his grandmother died from breast cancer. The impact of that loss altered Gangjee’s life, turning him away from a corporate future as an industrial chemist and propelling him onto the path of a medicinal chemist dedicated to fighting cancer.
