Ex-Californians bring cancer fight to West Texas

By SARAH NIGHTINGALEAssociated Press Sunday, December 20, 2023

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In a crowded room at a sold-out 1998 conference, Pat Reynolds psyched himself up for one of the biggest talks of his career.

The researcher and doctor would tell the audience of 10,000 about his work on a new drug for neuroblastoma, a cancer of the nerve cells occurring most commonly in young children.

But when half the doctors walked out, not interested enough to stick around for his 15-minute talk, he was crushed.

His peers had little interest in curing childhood cancers — more rare than cancers plaguing adults and less profitable for the big pharmaceutical companies.

Seeing the fallen faces of his colleagues, Reynolds snatched a pen and jotted a list of adult cancers.

"These are the things we're going to have to work on if we're going to get any attention," he said to his deflated co-worker, Barry Maurer.

So they collaborated with other researchers, expanding their work on a promising neuroblastoma drug — fenretinide — to adult cancers.

Since then, the duo have had some success treating recurrent ovarian cancer and adult lymphoma, and are working to improve their results in prostate cancer patients.

Strengthening their commitment to adult diseases, the researchers moved last year from a children's hospital affiliated with the University of Southern California to Texas Tech's Health Sciences Center, which was expanding its cancer program.

Sweetening the deal was Proposition 15, a 2007 amendment to the Texas Constitution setting aside $3 billion in state funds for researchers working on cancer.

It was an easy move for Reynolds — an El Paso native who likes West Texas people and plains — and an easy sell to Maurer, who moved with his wife, their horses and many more critters to a farm north of Idalou.

Min Kang, an associate professor with a doctorate in pharmacy, and about 14 junior researchers and technicians came with the duo, promised by Tech's Chancellor Kent Hance their research pace would quicken and their daily commutes would shorten.

"In the area of Lubbock where I live, it can take seven or eight minutes to get to campus in bad traffic, instead of four," the chancellor told them during a recruitment dinner. For some of those listening, hourlong commutes in bumper-to-bumper traffic were a daily part of L.A.'s not-so-fast lanes.

Long before Reynolds and Maurer were recruited from Southern California to Lubbock, the results of their first trial in 1998 looked promising. And with only one reported side effect — temporary night blindness — the drug rolled steadily from a Phase 1 safety study into a Phase 2 trial, with more patients in more areas of the country.

One of those patients was then-6-year-old Nick Leslie, whose 2002 neuroblastoma diagnosis came in the form of a softball-size tumor growing in his adrenal gland, weaving itself around his veins and attaching to his pancreas.

When his Oklahoma doctors first found his tumor, it was too large and bloody to remove. So they fought it with five rounds of chemotherapy, hoping to shrink it for surgery.

But the cancer-killing chemicals didn't make it small enough for the operation, necessitating a course of radiation and two bone-marrow transplants.

"That'll make it go away," the doctors reassured his mom and dad, Lydia and Ted.

It didn't.

And even when tumor was small enough for surgical removal, parts of it hung on, clinging to Nick's veins for survival.

Treatment wasn't over.

In 2003, Nick had another surgery and two rounds of a different kind of chemotherapy. Each time, some of the cancer cells remained.

Tired and disappointed, the family acknowledged the cancer would always be there.

"There's a good chance he will relapse," doctors warned.

But in spring 2004, one of Nick's doctors told them about Reynolds' fenretinide trial and they quickly signed him up.

Nick swallowed the 25 large pills every day, washing them down with water and hoping enough of the poorly absorbed drug would get inside the cancer cells lurking in his abdomen.

For the first year, the pills made him tired. After that, they made it hard for him to see in the dark. After that, though, his cancer was gone.

Nick was one of a handful of kids who did well on the capsules. But for other kids, even 750 large, oil-filled pills every month couldn't deliver enough of the drug to kill their cancers.

If the researchers improved the absorption, they knew they'd see better results.

A company Maurer talked to at a 2002 San Francisco conference told him they'd developed a wax-like substance that would dissolve fenretinide, making it easier for the body to absorb.

The researcher blended the new wax with fat, sugar and flour, eventually patenting a formulation — called Lym-X-Sorb — that kids actually liked to eat.

"It's kind of like a raw cookie dough," Maurer explained to the researchers and patients he worked with.

With Maurer's concoction in hand, a 2006 clinical trial sponsored by the New Approaches to Neuroblastoma Therapy consortium kicked off, again enrolling only those children who had relapsed on other medicines.

When the researchers shared their results at a recent conference, they reported them in the stoic manner expected of scientists: Twenty percent of their patients had fought off their cancers and another 20 percent saw no new growth.

On the inside, though, their spirits were high. Because the initial results were remarkable.

Reynolds and Maurer didn't spend long celebrating their results — there was still plenty to be done in the lab.

The data from the phase 1 Lym-X-Sorb trial helped them optimize the dosage for a second, larger phase of the trial, which they hope to find funding for soon. They are also combining fenretinide with other drugs — which may make it more effective — and are working on delivering the drug straight into patients' veins.

Without the financial support of a pharmaceutical company or large organization, though, the researchers will struggle to move their research from less expensive phase 1 trials to larger, more costly phase 2 studies.

In December, they started a company — called CerRx — to help them get their drugs from phase 1 to phase 2 trials, a gap scientists sometimes called the "valley of death" for new medicines.

And while Nick puts a six-year fight behind him, battling on the soccer and baseball fields instead, his cancer warriors go on.

The scientific discoveries that cured Nick created questions that will fuel their work for years.

The cancer researchers at Tech — also working with people at University Medical Center and Covenant — hope to build on the work started in California and create more stories like Nick's.

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