AACR: Progress treating pancreatic cancer, immunotherapy for head and neck cancers, potential biomarker for aggressive neuroendocrine carcinomas and more

UCLA investigators present the latest cancer research at the American Association for Cancer Research annual meeting April 5 to 10 in San Diego
Cancer with the cancer cell and the epigenetics with the DNA helix. Image credit: Shutterstock.

Investigators from the UCLA Health Jonsson Comprehensive Cancer Center will discuss the latest breakthroughs and cutting-edge science at the annual meeting of the American Association for Cancer Research (AACR), which attracts more than 20,000 oncology professionals from around the world.

The annual meeting will feature more than 40 regular, late-breaking and clinical trial abstracts from UCLA physicians and scientists, who will present their latest work in key areas of translational and basic scientific research, including new compounds and drug targets, combination immunotherapy approaches, updated organoid models, survivorship research and more. 

Dr. Deborah Wong, assistant clinical professor of medicine at the David Geffen School of Medicine at UCLA, will present findings from the IMvoke010 clinical trial (abstract CT009), which is a double-blinded randomized trial of atezolizumab after definitive local therapy vs placebo in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. The results will be highlighted during the during the Clinical Trial Plenary Session on April 7 from 3:30 to 5:30pm PT in Hall GH.

Dr. Zev Wainberg, professor of medicine at the David Geffen School of Medicine at UCLA and co-director of the UCLA Health GI Oncology Program, will share results from of a pilot study looking at neoadjuvant modified FOLFIRINOX plus nivolumab in borderline resectable pancreas cancer (abstract CT031). The findings will be presented during the Clinical Trials Minisymposium on April 8 from 2:30 to 4:30pm PT in Hall GH.

Alice Soragni, assistant professor in the department of Orthopaedic Surgery at the David Geffen School of Medicine at UCLA, will be chairing the Novel Experimental Models for Functional Precision Genomics session (AT05) on Monday, April 8 at 12:30pm PT in ballroom 20 CD. Soragni will also be presenting a talk on heterogeneity and genetic diversity in patient-derived organoid models from rare benign and malignant tumors during the session.

Additionally, Dr. Owen Witte, the founding director emeritus of the UCLA Broad Stem Cell Research Center, is being recognized with the 2024 AACR Award for Outstanding Achievement in Blood Cancer Research. Witte is being recognized for his unprecedented contributions to elucidating the role of tyrosine kinases in hematologic malignancies and for his pivotal role in developing novel cancer treatments. Witte’s award lecture will be held on Tuesday, April 9, at 4:30pm PT.

Highlights of noteworthy presentations at AACR that are led by UCLA researchers include:

Abstract 6574: UCHL1 is a molecular indicator and a therapeutic target for neuroendocrine carcinomas

A team of researchers led by Dr. Tanya Stoyanova, associate professor of molecular and medical pharmacology and urology at the David Geffen School of Medicine at UCLA, identified a protein called UCHL1 as a potential biomarker and therapeutic target for aggressive neuroendocrine carcinomas and a childhood cancer, neuroblastoma. Neuroendocrine carcinomas include neuroendocrine prostate cancer and small cell lung cancer. In the study, the team found that UCHL1 levels are significantly higher in tissues from patients with these neuroendocrine cancers and neuroblastoma. When UCHL1 is reduced or inhibited with small molecule inhibitors, the tumor growth and metastasis of these cancers decrease. The team also demonstrated that UCHL1 has a dual role in promoting cancer progression. It maintains the neuroendocrine characteristics of the tumor and influences the regulation of specific proteins involved in cancer growth. UCHL1 stabilizes a protein called POM121, which affects the transport of key transcriptional factors within the cancer cells. Additionally, UCHL1 binds to and degrades another important protein, p53, known to suppress tumor growth. This work suggests that UCHL1 may represent a common target for drug development in neuroendocrine cancers and neuroblastoma based on its higher expression in these tumors compared to non-neuroendocrine tissues, and also be used a potential molecular indicator for diagnosis and monitoring treatment responses in neuroendocrine carcinomas and neuroblastoma.

Stoyanova will present the findings during the Molecular, Preclinical, and Clinical Endocrinology 3 Minisymposium Session on Tuesday, April 9 from 2:30 to 4:30pm PT in room 5.

Abstract 6550: Biopsy analysis of trial S1616: Ipilimumab plus nivolumab versus ipilimumab alone in patients with anti-PD-1 refractory melanoma

To better understand the effectiveness of the combination treatment of two immunotherapy drugs ipilimumab and nivolumab for treating patients with melanoma, UCLA researchers analyzed biopsies taken from patients before and during treatment to understand the molecular and spatial characteristics of the tumors. The team found patients whose cancer responded well to the combination therapy had specific genetic and immune features at the start, including increased expression of genes related to various biological processes. Biopsies from these patients also showed changes indicative of tumor regression, such as reduced gene expression of certain pathways and increased infiltration of active immune cells. In contrast, for patients whose cancer did not respond to the treatment, the biopsies showed persistent exhausted immune cells and specific immune cell populations associated with tumor progression. This suggests that the addition of ipilimumab to the treatment helped some patients by promoting tumor-reactive immune cell infiltration and reducing suppressor cell activity, resulting in tumor regression with distinct genetic features. However, patients whose tumors progressed on the combination therapy lacked these positive changes and exhibited different immune dynamics.

Katie Campbell, adjunct assistant professor in the department of medicine at the David Geffen School of Medicine at UCLA, will present the findings during the Immuno-oncology Minisymposium Session on Tuesday, April 9 from 3 to 5pm PT in ballroom 20 CD.

Abstract 1220: Deep mutational scanning of EGFR reveals potential domain-specific TKI sensitivities in lung cancer and glioblastoma

New research led by Tikvah Hayes, assistant professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, identified new functional mutations in epidermal growth factor receptor (EGFR), a protein often found mutated in lung cancer and glioblastoma, highlighting the potential of EGFR inhibition as a treatment for cancers with specific mutations in the extracellular domain. To better understand the effects of different mutations in EGFR and how these mutations impact the response to drugs targeting EGFR, the team performed a comprehensive mutational analysis of EGFR function. The team created various mutations in EGFR and tested around 22,500 different variants in lung cancer cells dependent on EGFR. The results showed that certain mutations, especially in specific regions of EGFR, made the cancer cells less responsive to erlotinib, a first-generation EGFR inhibitor. They also found some variants in the extracellular domain of EGFR, for which there are currently no approved targeted therapies, responded well to another EGFR inhibitor called dacomitinib. The researchers also observed that a couple of glioblastoma patients with a particular mutation in the dimerization domain of EGFR had stable disease after dacomitinib treatment. 

Hayes will present the findings during the Biological Therapeutic Agents Minisymposium Session on Sunday, April 7 from 3 to 5pm PT in room 15.