Researcher Seeks Cancer Treatments Without Side Effects

TUCSON, Ariz. – The horrible side effects of chemotherapy treatments for cancer patients are legion.

The toxic chemicals that flood the patient's body to kill cancer cells can cause extreme nausea, muscle pain, flulike symptoms and a host of other ailments. They also kill healthy cells.

Now a University of Arizona scientist has gone off research's beaten path in his efforts to develop breakthrough therapies for cancer and other diseases that will cause no harm while doing good.

Current chemotherapy drugs focus on targeting proteins responsible for a cancer's growth, said Laurence Hurley, the UA Howard Schaeffer endowed chair in pharmaceutical sciences and associate director of the BIO5 Institute.

Doctors have long pumped people full of poisonous drugs — cytotoxins — to kill off individual cancer cells, with healthy cells also paying the ultimate price.

By developing a way to look at strands of human DNA in three dimensions, and targeting the DNA with cancer therapies aimed at selected subcell targets, Hurley hopes to cut out the negative side effects of cancer treatments.

Hurley likened the project to identifying the "lock" that controls cell growth and developing a drug "key" to secure the lock and prevent the growth of cancer. By turning off the cancer cell, disease growth is halted, and healthy cells are unharmed, he said.

"The concept around this idea is completely new," Hurley said. "It's a new frontier."

Hurley received a new type of National Institutes of Health grant designed to develop huge health benefits from "wild and crazy" exciting new ideas, said Laurie Tompkins, director of National Institutes of Health's EUREKA (Exceptional, Unconventional Research Enabling Knowledge Acceleration) program.

NIH, which promotes biomedical research, has funded many "conservative" research efforts but has tended to shy away from backing proposals for groundbreaking, innovative, "edgy" projects.

"But every now and then, someone has a really strange idea; if it works it would be really wonderful," she said.

Hurley was the first of 40 researchers funded by EUREKA, said Tompkins, who is with NIH's National Institute of General Medical Studies in Bethesda, Md.

Hurley, was awarded $200,000 annually for four years.

The money will be used to test his theories. If they are correct, additional funding will be needed to bring the new therapy to market.

The funding will allow Hurley and his team to look at three-dimensional "knots" in DNA called receptors and target them more efficiently to fight the disease.

Drugs are then designed to bind these receptors and turn off cancer genes selectively, Hurley said.

"We want to be able to kill cancer without harming any healthy cells," Hurley said from London, where he gave a presentation on his research at the University of London. "With the three dimensions, we have a much greater ability to differentiate between normal cells and cancer cells."

He compared his ongoing research efforts to a mission to Mars.

Hurley's first generation cancer drug — Quarfloxin, now in Phase 2 clinical trials to prove safety and efficacy — allows the treatment to know where Mars, the target, is.

Second-generation therapies — which Hurley is developing with funding from Science Foundation Arizona — offer additional details to allow a landing on a specific place on Mars, rather than just targeting the entire planet, he said.

And the third generation therapy, which the EUREKA grant will fund, will offer sophisticated information on the target's topography.

This will allow doctors to be much more selective in direction where the toxic cancer-killing agents go, he said, which will avoid harming healthy cells.

Hurley has begun working on the third phase project, with three researchers — Haiqing Yu, Danzhou Yang and Vijay Gokhale — in place and another due to arrive by year's end at his lab in BIO5.

From past experience, it takes three to four years to develop an idea into something ready for human testing, Hurley said, adding clinical trials can take five or six years.

"We are going into the unknown, we are going to see if we can push the envelope to something that is more difficult and has never been done before, and it is inherently more risky," he said.

Hurley long ago chose fighting cancer as his life's work after his father died of pancreatic cancer.

"In 1975, I made a pledge that I was going to do my best to do something about this disease," he said.

Hurley's newest project has broad applications beyond cancer, Tompkins said, which made it attractive to the EUREKA selection committee.

"This is good for basic research and a wide variety of clinical research," Tompkins said. "It is indeed innovative, with a unique strategy for screening for drugs that literally turn one gene, and one gene only, off. That's the Holy Grail.

"It could be cancer, cystic fibrosis, heart disease or anything else," she said. "If he can do it with one kind of gene it can do it with any gene."