With 10 prestigious publications that collectively cover basic cancer biology, translational efforts, clinical investigation, epidemiology, and prevention, the journals of the American Association for Cancer Research (AACR) are trusted channels for rigorously vetted discoveries spanning from bench to bedside. And every year the AACR Publications Program selects its AACR Journal Awards to celebrate science published in the past few years that has shown its staying power, honoring researchers whose studies have begun to mature under the scrutiny of the oncology community and are already influencing their respective domains.
The work of the 2025 AACR Journal Award recipients—three of whom received Early Career Awards—showcased insights with the potential to inform approaches to cancer prevention and care worldwide, including blood-based biomarkers to guide lung cancer immunotherapy, the bacterial microbiome in pancreatic cancer, curbing blood cancer risk associated with clonal hematopoiesis, and how metabolic plasticity helps breast cancer evade therapy.
“The editorial team from each of the journals carefully reviews recently published studies to choose the most impactful research that exemplifies stellar contributions to the fields covered by that journal,” said Robert Kruger, PhD, senior executive editor of the AACR journal Cancer Discovery.
To share more about their science and their stories, this year’s awardees sat down and spoke with Kruger. Watch their video interviews below and learn more about their research.
Courtney D. DiNardo: Paving the Way for a Promising Combination in Acute Myeloid Leukemia
The recipient of the 2025 Blood Cancer Discovery Award for Outstanding Journal Article is Courtney D. DiNardo, MD, MSCE, a professor of medicine at The University of Texas MD Anderson Cancer Center, who was recognized for “A Phase Ib/II Study of Ivosidenib with Venetoclax ± Azacitidine in IDH1-Mutated Myeloid Malignancies.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD-negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving ≥5 treatment cycles (N = 14). Median event-free survival and overall survival were 36 [94% CI, 23–not reached (NR)] and 42 (95% CI, 42-NR) months. Patients with signaling gene mutations appeared to particularly benefit from the triplet regimen. Longitudinal single-cell proteogenomic analyses linked cooccurring mutations, antiapoptotic protein expression, and cell maturation to therapeutic sensitivity of IDH1-mutated clones. No IDH isoform switching or second-site IDH1 mutations were observed, indicating combination therapy may overcome established resistance pathways to single-agent IVO.
Significance: IVO + VEN + AZA is safe and active in patients with IDH1-mutated myeloid malignancies. Combination therapy appears to overcome resistance mechanisms observed with single-agent IDH-inhibitor use, with high MRD-negative remission rates. Single-cell DNA ± protein and time-of-flight mass-cytometry analysis revealed complex resistance mechanisms at relapse, highlighting key pathways for future therapeutic intervention.
Sandra Misale: Revealing the Role of KRAS Amplifications in Colorectal Cancer Treatment Resistance
The recipient of the 2025 Cancer Discovery Early Career Award is Sandra Misale, PhD, an assistant professor of oncology at the Johns Hopkins University School of Medicine, who was recognized for “Molecular Characterization of Acquired Resistance to KRAS G12C–EGFR Inhibition in Colorectal Cancer.”
To be eligible for consideration for this award, articles must have been published in 2024 or 2025, and must be published within 12 years of applicants receiving their PhD/MD. Below, you can read the abstract for the award-winning paper.
With the combination of KRAS G12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRAS G12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRAS G12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance.
Significance: Clinical resistance to KRAS G12C–EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRAS G12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches.
Erika del Castillo: Pancreas-duodenum Connection Suggests Microbial Migration Influences Cancer
The recipient of the 2025 Cancer, Epidemiology, Biomarkers & Prevention Frederick P. Li Impact Award is Erika del Castillo, PhD, an associate scientist at Pharmaron, who was recognized for “The Microbiomes of Pancreatic and Duodenum Tissue Overlap and Are Highly Subject Specific but Differ between Pancreatic Cancer and Noncancer Subjects.”
To be eligible for consideration for this award, articles must have been published within the previous five years. Below, you can read the abstract for the award-winning paper.
Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.
Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples.
Results: Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects.
Conclusions: Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined.
Impact: Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.
Veronika Lutz and Christian Bauer: How Cytokine Signaling Suppresses Tumor-targeting T Cells
The recipients of the 2025 Cancer Immunology Research Award for Outstanding Journal Article are Veronika Lutz, PhD, a junior group leader at Philipps University Marburg, and Christian Bauer, MD, a researcher at the University of Marburg and head of the Department of Gastroenterology at Regional Hospital Deggendorf, MedizinCampus Niederbayern, who were recognized for “IL18 Receptor Signaling Regulates Tumor-Reactive CD8+ T-cell Exhaustion via Activation of the IL2/STAT5/mTOR Pathway in a Pancreatic Cancer Model.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
Intratumoral cytotoxic CD8+ T cells (CTL) enter a dysfunctional state characterized by expression of coinhibitory receptors, loss of effector function, and changes in the transcriptional landscape. Even though several regulators of T-cell exhaustion have been identified, the molecular mechanisms inducing T-cell exhaustion remain unclear. Here, we show that IL18 receptor (IL18R) signaling induces CD8+ T-cell exhaustion in a murine pancreatic cancer model. Adoptive transfer of Il18r−/− OT-1 CD8+ CTLs resulted in enhanced rejection of subcutaneous tumors expressing ovalbumin (OVA) as a model antigen (PancOVA), compared with wild-type OT-1 CTLs. Transferred intratumoral IL18R-deficient CTLs expressed higher levels of effector cytokines TNF and IFNγ and had reduced expression of coinhibitory receptors (PD-1, TIM-3, 2B4, LAG-3) and the transcription factors Eomes and TOX. Lower expression of coinhibitory receptors and TOX on IL18R-deficient versus IL18R-sufficient CD8+ T cells were confirmed in an orthotopic KPC model. IL18R-induced T-cell exhaustion was regulated by IL2/STAT5 and AKT/mTOR pathways, as demonstrated in an in vitro exhaustion assay. Concordantly, mice deficient in NLRP3, the molecular complex activating IL18, had decreased expression of coinhibitory receptors on intratumoral T cells and similar changes in signaling pathways at the transcriptome level. Thus, molecular pathways promoting T-cell exhaustion indicate an involvement of an NLRP3-expressing tumor microenvironment, which mediates IL18 release. The Cancer Genome Atlas analysis of patients with pancreatic carcinoma showed an association between NLRP3-mediated IL18 signaling and shorter survival. These findings indicate NLRP3-mediated IL18R signaling as a regulator of intratumoral T-cell exhaustion and a possible target for immunotherapy.
Tingting Zhai: Curbing Cancer Risk Associated With Blood Cell Mutations
The recipient of the 2025 Cancer Prevention Research Award for Outstanding Journal Article is Tingting Zhai, PhD, a senior principal statistician at Novartis, who was recognized for “Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased proinflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (NCT01327846) evaluated the neutralizing anti-IL1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab versus those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL1β blockade cooperating with CH mutations to modify the disease course.
Prevention Relevance: We reveal that administering canakinumab is associated with a decrease in non-hematological malignancies among patients with clonal hematopoiesis (CH) mutations. These findings underscore canakinumab’s potential in preventing cancer and provide proof of IL1β blockade collaborating with CH mutations to enhance its clinical benefits.
Minah Kim: Capturing How Compromised Tumor Vessels Keep T Cells Away
The recipient of the 2025 Cancer Research Early Career Award is Minah Kim, PhD, an assistant professor of pathology and cell biology at Columbia University, who was recognized for “Angiopoietin-2–Dependent Spatial Vascular Destabilization Promotes T-cell Exclusion and Limits Immunotherapy in Melanoma.”
To be eligible for consideration for this award, articles must have been published in 2024 or 2025, and must be published within 12 years of applicants receiving their PhD/MD. Below, you can read the abstract for the award-winning paper.
T-cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T-cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T-cell infiltration to the tumor core. The spatial regulation of ANGPT2 in whole tumor cross-sections was analyzed in conjunction with T-cell distribution, vascular integrity, and response to immunotherapy in syngeneic murine melanoma models. T-cell exclusion was associated with ANGPT2 upregulation and elevated vascular leakage at the periphery of human and murine melanomas. Both pharmacologic and genetic blockade of ANGPT2 promoted CD8+ T-cell infiltration into the tumor core, exerting antitumor effects. Importantly, the reversal of T-cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 immune checkpoint blockade therapy in immunogenic, therapy-responsive mouse melanomas, but it also rendered nonresponsive tumors susceptible to immunotherapy. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T-cell infiltration to the tumor core, coincided with spatial TIE2 signaling activation and increased vascular integrity at the tumor periphery where endothelial expression of adhesion molecules was reduced. These data highlight ANGPT2/TIE2 signaling as a key mediator of T-cell exclusion and a promising target to potentiate immune checkpoint blockade efficacy in melanoma.
Significance: ANGPT2 limits the efficacy of immunotherapy by inducing vascular destabilization at the tumor periphery to promote T-cell exclusion.
Moray J. Campbell: Disentangling Downstream Signaling of Diverse Vitamin D Receptors
The recipient of the 2025 Cancer Research Communications Award for Outstanding Journal Article is Moray J. Campbell, PhD, MS, a professor of cancer biology at Cedars-Sinai Medical Center, who was recognized for “African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function.
Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.
Joseph C. Murray: Blood-based Biomarkers to Predict Immunotherapy Outcomes in Lung Cancer
The recipient of the 2025 Clinical Cancer Research Early Career Award is Joseph C. Murray, MD, PhD, an assistant professor of oncology at The Johns Hopkins University School of Medicine, who was recognized for “Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer.”
To be eligible for consideration for this award, articles must have been published in 2024 or 2025, and must be published within 12 years of applicants receiving their PhD/MD. Below, you can read the abstract for the award-winning paper.
Purpose: Although immunotherapy is the mainstay of therapy for advanced non–small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect—especially in the setting of stable disease—calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE).
Experimental Design: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles.
Results: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE.
Conclusions: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.
Gary D. Luker: Stem Cells Prod Breast Cancer Cells to Consume Lactate and Evade Therapy
The recipient of the 2025 Molecular Cancer Research Award for Outstanding Journal Article is Gary D. Luker, MD, a professor of radiology and biomedical engineering at the University of Michigan, who was recognized for “Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor–Positive Breast Cancer.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer cells to resist standard therapy. We employed a coculture model of estrogen receptor–positive (ER+) breast cancer and mesenchymal stem cells (MSC) to model interactions of cancer cells with stromal microenvironments. Using single-cell endogenous and engineered biosensors for cellular metabolism, coculture with MSCs increased oxidative phosphorylation, intracellular ATP, and resistance of cancer cells to standard therapies. Cocultured cancer cells had increased MCT4, a lactate transporter, and were sensitive to the MCT1/4 inhibitor syrosingopine. Combining syrosingopine with fulvestrant, a selective estrogen receptor degrading drug, overcame resistance of ER+ breast cancer cells in coculture with MSCs. Treatment with antiestrogenic therapy increased metabolic plasticity and maintained intracellular ATP levels, while MCT1/4 inhibition successfully limited metabolic transitions and decreased ATP levels. Furthermore, MCT1/4 inhibition decreased heterogenous metabolic treatment responses versus antiestrogenic therapy. These data establish MSCs as a mediator of cancer cell metabolic plasticity and suggest metabolic interventions as a promising strategy to treat ER+ breast cancer and overcome resistance to standard clinical therapies.
Implications: This study reveals how MSCs reprogram metabolism of ER+ breast cancer cells and point to MCT4 as potential therapeutic target to overcome resistance to antiestrogen drugs.
Analisa DiFeo: Cornering Ovarian Cancer by Cutting Off Dual Routes of DNA Damage Repair
The recipient of the 2025 Molecular Cancer Therapeutics Award for Outstanding Journal Article is Analisa DiFeo, PhD, a professor of pathology and of obstetrics and gynecology at the University of Michigan, who was recognized for “Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.”
To be eligible for consideration for this award, articles must have been published within the previous two years. Below, you can read the abstract for the award-winning paper.
High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061–induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.
