Research Updates
AACR conferences and journals feature forward-looking findings poised to make an impact.
Treatment Advances Presented at the San Antonio Breast Cancer Symposium®
The San Antonio Breast Cancer Symposium (SABCS), which was held December 9-12, 2025, in partnership between UT Health San Antonio and the American Association for Cancer Research® (AACR), featured new approaches for treating various types of breast cancer.
For early-stage, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, endocrine therapies, such as tamoxifen and aromatase inhibitors, have been the standard of care for about three decades. In the phase III lidERA trial, patients with this breast cancer subtype who received the investigational oral selective estrogen receptor degrader (SERD) giredestrant were 30% less likely to have invasive disease progression after a median follow-up of 32.3 months compared with those on standard-of-care endocrine therapies. These results could place “giredestrant as a new standard in endocrine therapy,” according to Aditya Bardia, MD, MPH, the study’s presenter and director of translational research integration at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.
Findings from the phase III HER2CLIMB-05 trial, also presented at SABCS, showed that the addition of tucatinib (Tukysa) to first-line maintenance treatment of trastuzumab (Herceptin) and pertuzumab (Perjeta) delayed disease progression in patients with HER2-positive metastatic breast cancer. The addition of tucatinib reduced the risk of disease progression or death by 44.6% in patients with HR-negative metastatic breast cancer and 27.5% in those with HR-positive disease. In the subset of patients with brain metastases, adding tucatinib also nearly doubled the time it took for cancer to progress in the brain or for death from any cause.
Several studies also showed that treatment de-escalation may be a safe option for some patients. In the BOOG 2013-08 phase III trial, skipping sentinel lymph node biopsy did not compromise survival in some patients with early-stage HR-positive, HER2-negative breast cancer. And in the phase III Alliance A011104/ACRIN 6694 trial, preoperative MRI did not impact five-year locoregional recurrence rates for early-stage HR-negative breast cancer.
Cutting-edge Technologies and Novel Targets
The AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics delivered an “embarassment of riches” in investigational therapeutics research, according to conference cochair Ryan Corcoran, MD, PhD, of Mass General Research Institute in Boston. The conference, held October 22-26, 2025, featured promising early results for the DLL3-targeted therapy zocilurtatug pelitecan for extensive-stage small cell lung cancer, the bispecific antibody zenocutuzumab (Bizengri) targeting HER2 and HER3 to treat certain forms of bile duct cancer, and the PPARG inhibitor FX-909 for advanced bladder cancer.
While each of those therapeutics targeted a mutation known to drive cancer, other approaches used cutting-edge technology to circumvent this need. For example, regulated induced proximity targeting chimeras (RIPTACs) bring a target protein expressed in cancer cells closer to an essential protein needed for that cell’s functioning, and disrupts the essential protein, thus killing the cancer cell. In the case of HLD-0915, BRD4 is brought near the androgen receptor (AR), which is expressed in many cases of castrate-resistant prostate cancer for the selective killing of cancer cells. In a phase I/II study, antitumor activity was observed whether or not AR alterations were driving the cancer.
Another technology, called HELICON, could help overcome challenges in targeting the so-far “undruggable” WNT/β-catenin cell signaling pathway. While most approaches attempt to target the glycogen synthases in this pathway, FOG-001 uses HELICONs to inhibit the most downstream step of this pathway, which may allow any mutation in the pathway to be targeted.
An Investigational Drug Helps Some CLL Patients Stop Daily Treatments
Bruton’s tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of chronic lymphocytic leukemia (CLL); however, patients typically must stay on these therapies indefinitely. But a study published in the AACR journal Clinical Cancer Research found that adding the investigational antibody ianalumab (VAY736), which targets the B-cell activating factor receptor (BAFR), to the BTKi ibrutinib (Imbruvica) allowed some patients with CLL to discontinue daily therapy.
In the phase I trial, 17 of the 39 enrolled patients were able to stop taking ibrutinib and remain off therapy for one to two years. The overall response rate was nearly 60%, and undetectable measurable residual disease in the blood or bone marrow was 43.6%.
“Taking a medicine every day can be a reminder of sickness for patients, so it is very symbolic for patients with blood cancers to be able to go off therapy,” said the study’s senior author John C. Byrd, MD, who was chair of the Department of Internal Medicine at the University of Cincinnati College of Medicine and is currently the director of the UPMC Hillman Cancer Center in Pittsburgh.
Conference Explores Causes of Early-onset Cancers
In December 2025, AACR held the first-ever AACR Special Conference: The Rise of Early-onset Cancers—Knowledge Gaps and Research Opportunities. Cancer incidence in individuals under 50 has increased more than 15% since 2000. “What is especially concerning is that these young adults are presenting with metastatic disease or advanced local disease that often is deadly,” conference cochair Elizabeth M. Jaffee, MD, FAACR, told Cancer Research Catalyst, the AACR’s official blog. “We wanted to examine the topic of early-onset cancer from multiple angles,” added the AACR Past President and deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine in Baltimore.
At the conference, attendees examined potential mechanisms driving early-onset cancers. Among the reasons discussed was obesity—a known cancer risk factor—and how younger generations are spending more years obese before turning 35, which corresponds with rising early-onset cancer incidence. Another potential factor discussed was colibactin, a toxic molecule produced by a subset of E. coli. When colibactin damages DNA, it leaves behind a signature called SBS88, which is more often found in cases of early-onset colorectal cancers. Still, researchers stressed that much more research is needed to understand what is causing this rise and why.
Obesity-associated Cancers on the Rise in Puerto Rico
A study presented at the 18th AACR Conference on the Science of Cancer Health Disparities, held September 18-21, 2025, showed a significant increase in the number of obesity-related cancers in Puerto Rico. Between 2000 and 2022, the average annual percentage change (AAPC) of obesity-related cancers was 1.4% while non-obesity-related cancers remained stable. The highest increase was seen in women under 50 with a 4.9% AAPC among those 30 to 39, and a 4.6% AAPC in those 40 to 49.
Carola T. Sánchez-Díaz, MS, PhD, the study’s presenter and an assistant investigator in the Division of Cancer Control and Population Sciences at the University of Puerto Rico Comprehensive Cancer Center in San Juan, said further research is needed to understand the unique challenges faced by Puerto Ricans, as well as public policies to support healthier living and increased awareness about cancer screening.
Cancer Survival Improves in Medicaid Expansion States
In 2014, an Affordable Care Act (ACA) provision went into effect that allowed states to expand Medicaid eligibility to adults with incomes up to 138% of the federal poverty guidelines. States that adopted this Medicaid expansion saw survival rates for cancer patients improve, according to a study published in the AACR journal Cancer Discovery.
The study used a difference-in-differences (DD) design to compare data from states during 2007-2008—a period prior to Medicaid expansion—with data from 2014-2015. States that expanded Medicaid had significant DD improvements for both cause-specific (2.55 percentage points) and overall survival (3.03 ppt). Further, overall survival improved among non-Hispanic Blacks (1.05 ppt) and non-Hispanic whites (0.57 ppt), as well as in high-poverty areas (1.69 ppt).
Currently, 40 out of 50 states and the District of Columbia have enacted Medicaid expansion, with Alabama, Florida, Georgia, Kansas, Mississippi, South Carolina, Tennessee, Texas, Wisconsin, and Wyoming being the exceptions.
“These findings underscore the importance of expanding Medicaid in the 10 remaining non-expansion states and protecting expansion in the states that have already implemented it,” said the study’s lead author Elizabeth Schafer, MPH, an associate scientist at the American Cancer Society.
Journals Welcome New Editors-in-Chief
The American Association for Cancer Research® (AACR) announced the appointments of three new editors-in-chief joining two of AACR’s ten highly esteemed journals.
Cancer Immunology Research
Elizabeth M. Jaffee, MD, FAACR, and Antoni Ribas, MD, PhD, FAACR, have been selected as the editors-in-chief of Cancer Immunology Research.
Dr. Jaffee is the Dana and Albert “Cubby” Broccoli Professor in Oncology and deputy director of the Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins University in Baltimore, as well as inaugural director of the Convergence Institute and associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at SKCCC. She has been deeply involved in the AACR, including serving as the President of the organization in 2018-2019.
Dr. Ribas is professor of medicine, surgery, and molecular and medical pharmacology at the University of California Los Angeles (UCLA), as well as director of the Tumor Immunology Program at the UCLA Jonsson Comprehensive Cancer Center and director of the Parker Institute for Cancer Immunotherapy Center at UCLA. Dr. Ribas has also been involved in the AACR, including serving as the President of AACR in 2020-2021.
Cancer Immunology Research publishes original articles reporting advances in cancer immunology and immunotherapy that span the spectrum of science and medicine, from basic investigations in host–tumor interactions to developmental therapeutics in model systems, early translational studies in patients, and late-stage clinical trials. The journal disseminates the latest developments in the field to cancer researchers across all disciplines, catalyzing work that yields better clinical outcomes.
Blood Cancer Discovery
Ross Levine, MD, FAACR, was selected as the editor-in-chief of Blood Cancer Discovery. Dr. Ross serves as editor-in-chief alongside founding editors-in-chief Riccardo Dalla-Favera, MD, FAACR, and Kenneth C. Anderson, MD, FAACR, who have led the journal with distinction since its launch in 2019. Dr. Levine is chief scientific officer of Memorial Sloan Kettering Cancer Center in New York City, where he also holds the Edward P. Evans Endowed Chair for Myelodysplastic Syndromes. In addition, he is a professor of medicine at Weill Cornell Medical College.
Blood Cancer Discovery publishes original research articles and briefs, as well as perspectives and reviews of broad interest, that represent major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The journal’s scope includes genetic, immune, metabolic, microenvironmental, and systemic factors driving oncogenesis and therapy resistance; new therapies, diagnostic tools, and biomarkers; and computational and machine learning approaches to personalized medicine—from preclinical proof of concept to clinical trials and real-world evidence.
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