Tumors that become hypoxic, a condition depriving the region of an adequate oxygen supply, become resistant to chemotherapy and radiotherapy.

"This is a huge problem in the treatment of patients with cancer. As tumors progress, they have regions that are not well perfused with blood vessels and tumors become hypoxic." said Wafik S. El-Deiry, M.D. Ph.D., American Cancer Society Research Professor, Rose Dunlap Professor and chief of hematology/oncology, Penn State College of Medicine.

Dr. El-Deiry and his colleagues reports that the drug sangivamycin-like molecule 3 (SLM3) helps keep tumor cells from multiplying in lab mice, reported in the journal Cancer Research.

Researchers found that treating tumors in lab mice with SLM3 inhibits two key enzymes :(GSK-3ß) which regulates cell growth and cell death, and enzyme (CDK1) which regulates cell division and blood vessel growth, when the mice were treated with SLM3 the tumors which were previously found to be resistant to chemotherapy, died.

"While pure inhibition of GSK-3ß can promote cell proliferation, the combination of GSK-3ß and CDK-1 inhibition not only inhibits cell proliferation but also promotes cell death," said El-Deiry.

To find SLM3, the researchers screened a chemical library looking for molecules that induce apoptosis "cell death" in hypoxic tumor cells. SLM3 does that, and the researchers found eight molecules whose structures were similar.

"The bottom line is the molecules actually work to shrink tumors when these molecules are combined with chemo or TRAIL therapy," El-Deiry said. "We think that these are important observations that need to be tested further in the clinic."