Gertz and team receive large science grant (P01) for understudied endometrial cancer
Jay Gertz, PhD, program leader at Huntsman Cancer Institute and professor of oncological sciences at the University of Utah (the U), has received a program project grant from the National Cancer Institute to advance the study of hormone therapy for endometrial cancer. Gertz is the co-principal investigator of the project, alongside Kimberly Leslie, MD, at the University of New Mexico Comprehensive Cancer Center.
The five-year, multi-institutional project will study which progestins, or synthetic progesterones, could be most effective as a treatment for endometrial cancer as well as which patients are most likely to benefit. Gertz says progestins have been shown to be effective as a single treatment in over half of endometrial cancer patients, but they aren’t often used.
Gertz and the team developed the grant in partnership with Huntsman Cancer Institute’s Breast and Gynecologic Research Advocate Committee. The volunteer committee is comprised of patients and survivors who had breast, ovarian, endometrial, and cervical cancers. Gertz says that endometrial cancer is increasing in incidence, but the disease remains understudied. The support and feedback from the committee were essential in crafting a project that will best serve patients now and in the future.
The University of New Mexico, Holden Comprehensive Cancer Center at the University of Iowa, and the University of Kansas Cancer Center are the main collaborating institutions on this project.
New review highlights gaps in skin cancer care
A recent review by Elliot Asare, MD, MS, CMQ, FACS, investigator at Huntsman Cancer Institute and assistant professor in the Department of Surgery at the U, found that older adults and those living in rural areas are more likely to face delays in getting treatment and worse outcomes for dangerous types of skin cancer. Asare’s research, published in Surgical Clinics of North America, focused on melanoma, advanced squamous and basal cell skin cancers, and Merkel cell carcinoma.
The average age of diagnosis for melanoma is 66 years, and older individuals make up the largest percentage of patients who die from the disease. But in his review, Asare found that older adults are less likely to receive standard-of-care treatments for aggressive skin cancers. Barriers to care may include competing health conditions, difficulties getting to appointments, and not noticing changes in the skin.
Asare found that rural patients are more likely to present with higher rates of metastatic disease at the time of diagnosis. He also highlights that rural patients are less likely to wear sunscreen and live far from skin care experts. Both factors contribute to increased UV damage and later diagnoses.
Understanding skin cancer patterns in this patient population is particularly important for Huntsman Cancer Institute, whose physicians care for patients from across the rural Mountain West. The region also has one of the highest rates of melanoma in the country.
“High-risk skin cancers don’t affect everyone the same way. To save lives, we need to understand who’s being left behind—and why,” says Asare. “We need to meet patients where they are, and make sure everyone has a fair chance at early diagnosis and the best care possible.”
Researchers develop novel T-cell platform for multiple myeloma
Researchers at Huntsman Cancer Institute have developed and evaluated a novel immunotherapy system designed to address the limitations of current T-cell engaging therapies for the treatment of patients with multiple myeloma. The MATCH program—Multi-Antigen T-cell Hybridizers—is a flexible two-component system that can adapt to the unique molecules, or antigens, found on patients’ cancer cells. The MATCH platform, evaluated in preclinical models, occurs in two parts. First, the therapy attaches to cancer cells. The second finds activated T cells, brings them to cancer cells, and kills them. A key feature of MATCH is that it only exerts the killing function when the target expression is present, sparing healthy tissue.
The research team led by Jindřich Henry Kopeček, PhD, DSc, Huntsman Cancer Institute investigator and distinguished professor of biomedical engineering and molecular pharmaceutics at the U, and Jiyuan Yang, PhD, Huntsman Cancer Institute investigator and professor of molecular pharmaceutics at the U, developed the system in response to obstacles in multiple myeloma care. Multiple myeloma makes up 13% of all blood cancers in the United States. Immunotherapy, harnessing patients’ own immune system to combat cancer cells, has been shown to be a promising treatment for the disease. But patients can develop resistance to the therapy or experience side effects like cytokine release syndrome. Cytokines are proteins that regulate immune responses. When they are rapidly released into the body, patients develop flu-like symptoms that can be mild or life-threatening.
“There are limited treatment options for multiple myeloma, especially in cases that either do not respond to therapy or have become resistant to therapy,” says Kopeček, co-primary investigator of the study. “We hope that the MATCH system will improve the efficacy of this type of treatment by decreasing cytokine release and personalizing the treatment based on the biomarker profile of the patient’s cancer.”
Douglas Sborov, MD, MS, director of Huntsman Cancer Institute’s Hematology Disease Center and Plasma Cell Dyscrasias Program and associate professor of internal medicine and molecular pharmaceutics at the U, also contributed to the study. Shannuo Li, MS, doctoral student in molecular pharmaceutics, is the first author.
Cell “identity crisis” impacts tumor growth, treatment resistance in lung adenocarcinoma
Cells throughout the body have specialized functions unique to their purpose and location. This is known as the cell’s identity. Shifting cell identity can influence tumor growth in lung adenocarcinoma and can also negatively impact patient responses to targeted therapies seen as promising new treatments for patients. Eric Snyder, MD, PhD, Huntsman Cancer Institute investigator and professor of pathology at the U, and Gabriela Fort, PhD, Huntsman Cancer Institute investigator, found that lung cancer cells sometimes abnormally express the protein HNF4α, which is associated with gastrointestinal (GI) tissue. HNF4α imparts a hybrid identity on the cancer cells, which contributes to abnormal growth associated with cancer.
“Basically, the lung cells start to act and look like gastric cells, and the cells take on more than one function,” says Fort. “It’s like a cell having an identity crisis, which, for reasons we are still investigating, drives tumor growth.”
They also discovered that the presence of HNF4α in these cells could blunt the effectiveness of therapies targeting the KRAS protein. Targeted therapies inhibiting KRAS are an emerging treatment option for many lung cancer patients, as well as other cancer types. Fort and Snyder believe there’s a possibility that a drug targeting HNF4α will help patients respond to KRAS inhibitors more effectively.
Their findings may impact future drug development for thousands of cancer patients. According to the National Institutes of Health, lung adenocarcinoma is the most common lung cancer in the United States, and lung cancer remains the leading cause of cancer death in the country. Better molecular understanding of cancer cell function contributes to more personalized treatment methods.
“It’s very clear that for most cancers, a single drug won’t be enough,” says Snyder. “And it’s also clear that cellular identity affects response to therapy. So, the optimal therapeutic strategy is going to integrate both the genetics of the tumor, as well as its identity.”
The results of their research were published as the cover article in Genes and Development.
In Other News
Heloisa Soares, MD, PhD, Huntsman Cancer Institute oncologist and associate professor of internal medicine at the U, has been named medical director of Huntsman Cancer Institute’s growing theranostics program. Theranostics is a powerful strategy that uses radiopharmaceuticals to locate tumors and deliver targeted radiation directly to cancer cells. Jeffrey Yap, PhD, Huntsman Cancer Institute investigator and professor of radiology and imaging sciences at the U, will serve as research director of theranostics. Huntsman Cancer Institute’s Center for Quantitative Cancer Imaging will now be known as the Center for Quantitative Cancer Imaging and Theranostics, in recognition of the transformative power of theranostics in research and clinical care.
About Huntsman Cancer Institute at the University of Utah
Huntsman Cancer Institute at the University of Utah is the National Cancer Institute-designated Comprehensive Cancer Center for Utah, Idaho, Montana, Nevada, and Wyoming. With a legacy of innovative cancer research, groundbreaking discoveries, and world-class patient care, we are transforming the way cancer is understood, prevented, diagnosed, treated, and survived. Huntsman Cancer Institute focuses on delivering the most advanced cancer healing and prevention through scientific breakthroughs and cutting-edge technology to create pioneering cancer treatments beyond the standard of care today. We have more than 325 open clinical trials and 276 research teams studying cancer. More genes for inherited cancers have been discovered at Huntsman Cancer Institute than at any other cancer center. Our scientists are world-renowned for understanding how cancer begins and using that knowledge to develop innovative approaches to treat each patient’s unique disease. Huntsman Cancer Institute was founded by Jon M. and Karen Huntsman.