UC researchers working to make blood cancer a manageable illness

UC researchers working to make blood cancer a manageable illness

Collaborative process aims to bring new treatments to patients more efficiently

As blood cancers are constantly evolving and developing mutations that grow resistance to current treatments, researchers in the University of Cincinnati Cancer Center's Leukemia and Drug Development Lab (LDDL) are constantly working to bring new treatments to patients.

By identifying new mutations through patient samples, working with pharmaceutical companies in developing and testing molecules in the lab, and testing these compounds in patients through Phase 1 clinical trials, the team aims to make blood cancer research breakthroughs more efficient than ever before.

An ongoing battle

Blood cancers can be thought of like colorful sprinkles, with new treatments needed for each color, or mutation, that arises. Photo/Alexander Grey/Unsplash.

The Cancer Center's Erin Hertlein, PhD, said that in the absence of a curative therapy , the long-term goal is to make blood cancer a manageable chronic illness for these patients.

"I think the ultimate goal will always be to cure cancer, but the reality is that because cancer learns how to evolve and develop resistance, this isn't always achievable," said Hertlein, a Cancer Center researcher and associate professor in UC's College of Medicine. "But as we continue to learn more about how cancer evolves, we can anticipate this resistance. And when we can anticipate resistance, we are prepared to develop newer and better therapies, and we can adjust treatment strategies to overcome resistance."

Hertlein said the field often talks about "bench-to-bedside" research that moves new therapies from labs to clinics, but the LDDL also takes a "bedside-to-bench" approach.

"We learn from patients that are receiving these therapies what obstacles or barriers may arise, and we pivot and develop new ways to proceed," she said. "In this way, we are providing opportunities for patients to live long-term while managing their cancer. For some types of leukemia, while on treatment, patients can expect to have a normal lifespan."

Researchers essentially play an ongoing game of whack-a-mole, working to find safe and effective treatments for each new cancer clone - each new sprinkle color - and then starting the process over again when the next dominant, treatment-resistant mutation is identified.

The LDDL team has taken a page from the tech industry and works to fail fast if a line of research appears that it will not be fruitful. Being nimble and humble to move on from dead ends in research allows the team to get potential treatments to clinical trials more efficiently while also focusing on patient safety as the No. 1 priority.

"Support for cancer research comes from many sources, and whether it's NIH or private foundation funds, or philanthropy funds, our goal is to be good stewards of those funds and increase our chances of bringing the most effective therapies to patients," Hertlein said. "This means that we don't waste time or money on things that we can rule out as less potential to have clinical impact."

Erin Hertlein and her colleagues working in the Cancer Center's Leukemia and Drug Development Lab take discoveries from the research lab to the clinic and back again to accelerate discoveries and new treatments. Photo/UC Foundation.

Research in action

The lab recently focused on a common mutation called FLT-3, which up to 30% of patients with AML have. A standard FLT-3 treatment called gilteritinib was approved by the Food and Drug Administration in 2018, but as the cancer has evolved, some patients have developed resistance to it.

In a first agreement of its kind for the Cancer Center, the LDDL team partnered with pharmaceutical company Eilean Therapeutics to identify a new drug to treat the treatment-resistant cancer clone. In a multiyear process, LDDL researchers tested more than 60 compounds before landing on a new drug called lomonitinib that appeared to be the most effective in preclinical testing.

As an industrial-academic team, they can evaluate results and make decisions in near real time, allowing for favorable safety profiles to be established. These results were selected by peer review for presentation at national conferences hosted by expert hematologists.

Eilean recently received approval from the FDA and partnered with Blood Cancer United (formerly known as the Leukemia Lymphoma Society) to open a Phase 1 clinical trial testing lomonotinib's safety and efficacy in patients as an arm of the Beat AML master trial. These collaborations are a powerful tool to bring therapies to patients efficiently.

LDDL team members like research scientist Sara Elgamal, PhD, are constantly looking for new blood cancer mutations and potential treatments. Photo/UC Foundation.

The importance of patient samples

In the research process, Johnstone said the LDDL has an advantage by regularly utilizing blood samples from patients who have consented to participating in groundbreaking research at the Cancer Center's new Blood Cancer Healing Center, including newly diagnosed patients and those whose cancer has relapsed or recurred.

"Your resistance and relapse patients may never see the treatment that our group develops because it takes a cumulative of many patients to get there, but their samples are enrolled," she said. "It is just this continuous cycle of novel research and then resistance and relapse research."

While many academic health centers regularly use patient samples in their research labs, Johnstone said the volume of samples processed in the LDDL sets it apart. The team tests different drug compounds on patient-derived cancer cells and preclinical models developed using patients' cells.

"We have hundreds of samples saved, and we have access to national databases that we use regularly," Johnstone said.

Johnstone said the team is grateful to each patient who consents to provide samples, especially when some patients may never benefit from the research breakthroughs their own blood samples are helping move forward.

Lab members Carolyn Cheney, left, and Tom Sesterhenn, right, review data. Photo/UC Health.

"We collect whole blood from consented patients. We then separate blood into liquid and cellular components," Johnstone said. "We use everything. There is no waste. Each component becomes data points that are used in many different experiments. This helps us move science efficiently for patients and their families."

The comprehensive Blood Cancer Healing Center has the potential to make the process even more efficient, as researchers, clinicians, patients, caregivers and other stakeholders will all be located under one roof. Patient samples will only need to travel up a few floors to the new LDDL research space on the building's fourth floor, providing the potential to accelerate the next discovery even more quickly.

"We're bringing everyone to the same table, so it's not uncommon for me to be in an elevator with clinicians like Emily Curran or Zulfa Omer," Johnstone said. "And we can make a decision in that 30-second elevator ride. So we're making real-time decisions that aren't beholden to schedules. We're meeting regularly, we're meeting ad hoc, and so we can make those choices to drive treatments to patients faster."

Innovation Lives Here

Featured photo at top of Megan Johnstone working in the lab. Photo/UC Health.

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