A promising treatment for leukemia uses a patient’s own cells to recognize and attack cancer, but its potential side effects include seizures and even comas.
A hormonal therapy for prostate cancer works well until the cancer finds a workaround and becomes resistant.
A colorectal cancer treatment plan could save a life, but not if the patient must catch three buses for an appointment, can’t get a ride home after a procedure or can’t afford the prescription co-pays.
Three research fellows at Fred Hutch Cancer Center focusing on these problems won Young Investigator Awards this year from Conquer Cancer, the ASCO Foundation. They were honored at theAmerican Society of Clinical Oncologyannual meeting in Chicago last week.
The winners— Emily Liang, MD, Steve Blinka, MD, PhD, and Natasha Kwendakwema, MD — represent the wide range of research supported by the Hematology/Oncology Fellowship Program at Fred Hutch and the University of Washington.
The program helps physicians who have completed their residency launch academic research careers in hematology and/or oncology.
“The primary motivation of our fellowship is to train physicians for academic careers in basic science, translational research or clinical research, via a mentored-training program,” said program director Manoj P. Menon MD, MPH. “Although each of our fellows are highly motivated, each really benefitted from our program and our program benefitted from them.”
The award includes a one-year, $50,000 research grant.
“The winners of this prestigious award, and the mentors who guide their studies, represent the core of our mission to unite innovative research and compassionate care,” said Sara Hurvitz , MD, FACP, senior vice president and director of clinical research at Fred Hutch.
Helping patients tolerate a potentially transformative therapy
Liang, who was raised in the San Francisco Bay Area, found her research path after a rotation in the leukemia ward.
“What was most rewarding was getting to know the patients from all different ages and walks of life,” Liang said. “It’s a very long journey through that process.”
Her Fred Hutch fellowship included a year and a half of time-consuming clinical work.
“Despite that, Emily during those 18 months was extremely productive,” Menon said. “She published a number of manuscripts and presented on the national stage at multiple conferences, including the American Society of Hematology.”
Her research focuses on a therapy that tunes a patient’s own immune system to better fight cancer.
Chimeric antigen receptor-modified (CAR) T-cell therapy removes a patient’s T cells, genetically modifies them to better combat tumors, and then returns them to the patient.
“It engineers a patient’s own cells to recognize and attack the cancer,” Liang said.
It is a complex therapy that can only be administered at cancer centers such as Fred Hutch. Patients must be healthy enough to withstand the inflammatory side effects of the treatment, which can include fever, low blood pressure, confusion, seizure or even coma.
“You’re getting a treatment to try to cure cancer, but then you may die or suffer really severe consequences from the treatment itself,” Liang said.
A clinical trial is underway testing whether a medication used in rheumatoid arthritis can reduce the inflammation of CAR T-cell therapy. Liang will use her award money to fund experiments on samples from blood and lymph node tumors collected during the clinical trial.
Applicants for the Young Investigator Award must have mentors. Liang is the first fellow that hematologist-oncologist Jordan Gauthier, MD, MSc, has mentored in the program.
“Dr. Gauthier and I are interested in basically trying to reduce these side effects,” she said. “That way more patients can receive CAR T-cell therapy and people will do better when they’re getting the treatment.”
Liang also won support for her work this year from The Hartwell Innovation Fund, which supports high-risk/high-reward projects led by young investigators at Fred Hutch or UW Medicine. This year’s funding was made possible by Swim Across America, an annual event benefiting Fred Hutch.
She presented two studies at ASCO on predicting hematotoxicity (the adverse effect of a drug or agent on blood or bone marrow), which is a major cause of death following CAR-T cell therapy.
Other Fred Hutch-UW Hematology/Oncology fellows who presented work at ASCO this year:
- Jennifer Huang MD, PhD
- Natalie Miller MD, PhD
- Blossom Raychaudhuri, MD
- Ruben Raychaudhuri, MD
- Lauren Shih, MD
Finding a workaround to the workaround
Blinka, who was raised in the suburbs of Milwaukee, hopes to follow the path charted by his mentor, prostate cancer researcher and medical oncologist Andrew C. Hsieh, MD, to become a physician-scientist who works mostly in the lab, but still sees patients in the clinic.
“It helps you see what the clinical needs are, and you can go back to the lab and bridge that gap,” Blinka said. “You can see the toll that some of these therapies take on patients.”
Hsieh’s lab studies the process of translation control, which turns the information encoded in RNA into proteins. When this level of gene expression goes awry, it fuels tumors in prostate and bladder cancer.
“He’s one of the few guys focusing on this area,” Blinka said. “There’s a lot of opportunity there.”
Hormonal therapy is a common treatment for prostate cancer, but the cancer often finds a workaround and becomes resistant.
Blinka is looking for his own workaround to delay that resistance and extend the shelf life of hormonal therapy before patients must switch to less optimal, less tolerable treatments.
The compounds they’re using to slow resistance show promise in a laboratory setting, but they’re not ready for patients.
“So far the tools we use in the lab, they’re not druggable compounds,” Blinka said. “You would have to use them at way too high of a dose, they would be too toxic, you can’t get them into a suspension that you could actually give a human.”
He’ll use the award money for lab supplies to solve that problem.
“I think there’s a good chance we can find something and get it to clinic,” Blinka said.
Reducing financial toxicity
Winning a Young Investigator Award helps new researchers generate preliminary data that gives them a leg up in the increasingly fierce scramble for limited funding.
“It’s definitely a feather in the cap and provides pilot data— often a necessary thing to be optimally competitive for the next grant,” said Menon, a former fellow in the program who also won a Young Investigator Award.
The application process for the award is often the first time that fellows have applied for outside funding for their projects, which is where their mentors’ experience comes in handy.
That was the case for Kwendakwema, who was raised in Salt Lake City.
She said she couldn’t have written a persuasive application without her mentor, Veena Shankaran MD, MS, co-director of the Hutchinson Institute for Cancer Outcomes Research (HICOR).
“She’s done this successfully so many times, she has very good insight as to what are the things to prioritize, what are the things to really detail and explain in your project, what are the things to think through,” Kwendakwema said.
But it is her mentor’s expertise on how money troubles prevent cancer patients from getting the care they need— a circ*mstance known as “financial toxicity”— that most inspires Kwendakwema.
Some obstacles such as inadequate insurance or expensive prescriptions are well known, but other hurdles exist that those without financial hardship may take for granted, such as transportation, time off work, or an escort home after a procedure.
“People often have to catch multiple buses to get to their appointments,” Kwendakwema said. “That’s extra time that it takes, and they have to pay for the buses. All of it comes into play in people’s decision-making about what kind of care they can receive and when and how.”
Curious about new findings at the latest meeting of the American Society of Clinical Oncology?View highlights from oral presentations and poster sessions from Fred Hutch researchers.Fred Hutch at ASCO 2024
Kwendakwema will use her Young Investigator Award money to hire an analyst who can help her interpret information from theHICORdatabase.
She wants to study whether financial hardship, as seen in credit reports, might affect a patient’s ability to receive cancer treatment like chemotherapy, blood tests and CT scans.
She hopes the objective data, combined with what patients report themselves about their financial hardships, will provide a fuller picture of how money impacts treatment options. That data could help physicians anticipate problems and intervene sooner with support.
“This is the thing that I think about almost as much as thinking about what treatments to give my patients,” she said. “It doesn’t matter if you develop wonderful treatments if your patients can’t get them.”
That dedication was well represented at ASCO this year, Shankaran said.
“I am immensely proud that our fellows and junior faculty are being recognized by ASCO for all their hard work in addressing disparities in and financial barriers to high quality cancer care,” she said.
