City of Hope, one of the largest and most advanced cancer research organizations in the United States, will showcase its cutting-edge research at the upcoming American Association for Cancer Research (AACR) Annual Meeting. The event, scheduled for April 25-30, 2025, in Chicago, will feature more than 74 presentations from City of Hope researchers covering breakthroughs in artificial intelligence, precision medicine, immunotherapies, and novel treatment approaches.
Innovative Immunotherapy Shows Promise for Nasopharyngeal Carcinoma
A phase 3 clinical trial of penpulimab, a novel anti-PD-1 inhibitor, has yielded promising results for patients with recurrent or metastatic nasopharyngeal carcinoma. Dr. Aditya Shreenivas, a medical oncologist at City of Hope, will present data showing that patients who received penpulimab in combination with standard chemotherapy experienced cancer control for 9.63 months on average, compared to just 7.00 months for those who received chemotherapy alone – representing a 55% reduction in the risk of disease progression.
"What makes penpulimab unique is that it is an anti-PD-1 antibody with a modified structure designed to potentially improve efficacy while reducing immune-related side effects," said Dr. Shreenivas, who led the study at City of Hope, one of 46 trial sites worldwide. "This research supports use of penpulimab plus chemotherapy as a new first-line treatment option for patients with recurrent or metastatic nasopharyngeal carcinoma."
The FDA recently approved penpulimab in combination with cisplatin or carboplatin and gemcitabine for first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma, as well as a single agent for patients with disease progression after platinum-based chemotherapy and at least one other prior therapy.
Advanced Technologies Reveal Treatment Response Patterns
City of Hope researchers are employing cutting-edge spatial transcriptomic technologies to better understand treatment responses in various cancers.
Ovarian Cancer Immunotherapy Response
A team led by Jing Qian, a doctoral student in Dr. John D. Carpten's lab, used spatial transcriptomic technologies to map interactions between cancer and immune cells in high-grade serous ovarian cancer patients with different responses to immunotherapy. Their findings revealed differing immune cell behavior and composition in tumors with varied treatment responses.
"In the future, this approach could help identify patients who are more likely to benefit from immunotherapy and uncover new targets to improve treatment for those who don't respond," said Qian. "Ultimately, it pushes the field closer to precision immuno-oncology in high-grade serous ovarian cancer."
Prostate Cancer Ethnic Differences
Dr. Tanya Barauskas Dorff and her team used digital spatial profiling to study differences in tumor tissue from Hispanic and non-Hispanic patients with metastatic hormone-sensitive prostate cancer. They found differences in expression of certain proteins like Foxp3, PARP, and STING – all targets of specific cancer medications – between the two patient groups.
"This type of exploration in tissue samples from patients of diverse backgrounds may help uncover factors that could account for differences in treatment response," said Dr. Dorff. The team plans to compare their findings against treatment outcomes as they become available in early 2026.
AI-Enhanced Breast Cancer Prediction
Sydney Grant and Dr. Aritro Nath developed a powerful new AI-based approach to predict recurrence-free survival in breast cancer patients. By enhancing existing generative AI models to process a broader range of real-world patient data, they established an approach that enables more accurate and personalized predictions about cancer patient outcomes.
"This work could lead to new clinical tests used at the time of diagnosis to guide treatment decisions and bring us closer to truly personalized care," said Dr. Nath. "For example, these tools would help doctors identify which patients need more aggressive therapy and which patients could avoid overtreatment and unnecessary side effects."
Addressing Cancer Disparities Through Technology
Unique Genetic Changes in Hispanic and Latino Colorectal Cancer Patients
Dr. Enrique Velazquez Villarreal's lab has identified unique genetic changes in early-onset colorectal cancer among Hispanic and Latino patients that help explain how the cancer grows and spreads. Using DNA and RNA sequencing plus 10x Genomics Visium technology, the team gained insights into how cancer cells interact with the immune system in this patient population.
"This is the first study to look closely at the genetics of colorectal cancer in Hispanic and Latino patients from the Los Angeles area, a group that's often left out of cancer research," said postdoctoral fellow Francisco Carranza, who is first author on the study. "By understanding how colorectal cancer affects different populations, especially those who are often overlooked, we can help create better and more targeted treatments."
AI Tool for Inclusive Precision Medicine
Dr. Velazquez Villarreal will also present on his lab's development of a new precision medicine AI tool called the Precision Medicine Artificial Intelligence Agent (PM-AI). This conversational AI system can understand plain-language questions and automatically run complex data analyses, combining clinical information, genetic data, and social factors to make it easier for scientists to study cancer in a more complete and inclusive way.
"By making it easier to analyze large and complex datasets, PM-AI can help researchers and doctors discover which treatments work best for different groups of people," said Dr. Velazquez Villarreal. "This means patients could one day receive more personalized care based on their genetics, health history, and social conditions—leading to better outcomes for everyone, especially underserved communities."
Overcoming Treatment Resistance in ER+ Breast Cancer
Researchers led by Dr. Andrea Bild have discovered a new combination therapy approach to overcome resistance to cell cycle inhibitors in estrogen receptor-positive (ER+) breast cancer. Their study revealed that ER+ breast cancers resistant to cell cycle inhibitors undergo dynamic rewiring of both apoptosis and proliferative pathways to survive.
The team identified a promising combination of ribociclib (a cell cycle inhibitor) plus afatinib (a growth factor inhibitor) that can durably control breast cancer cell growth over time.
"Although cell growth-targeted drugs have improved outcomes for hormone-dependent breast cancer patients, resistance remains a major clinical challenge limiting their long-term benefit," said Dr. Bild. "Our research presents a novel strategy to enhance the durability and effectiveness of current treatments."
Leadership in Cancer Research
Several City of Hope leaders will chair key sessions at the conference:
Dr. David W. Craig, professor and founding chair of the Department of Integrative Translational Sciences, will chair the final plenary session on "Opportunities in Predictive Oncology" and present on using multiomics to investigate the unique genetic makeup of different cell populations in solid tumors.
Dr. Michael A. Caligiuri, former president of City of Hope National Medical Center, will chair a session on advances in the application of natural killer (NK) cells and present on "Innate immune lymphocytes, including NK cells." He will also chair a session on academic entrepreneurship focused on translating research from bench to bedside.
Dr. Hope Rugo, who recently joined City of Hope as director of its Women's Cancers Program, will present on managing toxicities from antibody-drug conjugates and serve as a discussant at the Clinical Trials Plenary Session on Biologics and T-cell Engagers.
"The extensive breadth and depth of research being presented at AACR by City of Hope's researchers exemplifies our commitment to making hope a reality for all cancer patients," said Dr. John D. Carpten, City of Hope's chief scientific officer. "We are proud to share our dedication to developing innovative technologies and treatments for improved care through a combination of scientific discovery, clinical ingenuity and compassion."
