Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy and has long been regarded as a therapeutic "drug graveyard", with modest gains from cytotoxic combination chemotherapy and numerous novel agents failing to show benefit in clinical trials. The quest to directly target RAS has moved from concept to reality with the FDA approval of daraxonrasib (Rasonque) for adults with metastatic PDAC who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. Here we discuss a wave of clinical trials that are poised to change this narrative and usher in the era of RAS-targeted therapy. Given the flood of compounds and combinations, we focus on therapies that have advanced to phase 3 clinical trials. Collectively, these studies demonstrate how RAS-targeted therapies are poised to transform the PDAC treatment landscape. The current generation of trials will determine whether these emerging strategies can translate into durable survival gains and turn PDAC from a "drug graveyard" into a drug haven for novel therapies.

Li-Fraumeni Syndrome (LFS) is caused by germline likely pathogenic/pathogenic variants in the TP53 gene which encodes the p53 tumor suppressor. LFS is a hereditary cancer predisposition syndrome (CPS) with significant lifelong multi-organ cancer risk. As one of the earliest described and less common CPS, knowledge of LFS has grown significantly over time through international collaboration. Future progress in the management of these patients is dependent upon clinical and research advances as facilitated by disease-specific patient/family meetings like the LFS Association bi-annual REACH meeting. This meeting brings together scientists, clinicians, LFS patients and their family members in a collaborative effort to explore challenges in the field. Major current areas of study in LFS include: (1) improving our understanding of specific p53 tumor suppressive functions necessary for cancer development, (2) developing novel classification systems for TP53 variants, (3) exploring more precise genotype-phenotype correlations, (4) defining the cancer spectrum to better inform risk prediction for patients, and (5) understanding the psychosocial implications of an LFS diagnosis. Areas of need were also identified, particularly the need for more precise and practical methods of cancer screening and innovative strategies for targeting the p53 pathway for cancer prevention or early tumor interception. This commentary reflects the major advances in understanding of LFS, including most up-to-date research in the field related to p53 biology, variant interpretation, and clinical care. Herein, we also review areas of late-breaking research and future directions in the field, as a "call to action" for LFS researchers and clinicians.

In November 2025, the U.S. FDA granted traditional approval to epcoritamab-bysp in combination with lenalidomide and rituximab (R2) for adults with relapsed or refractory follicular lymphoma (FL). Approval was based on EPCORE FL-1, a randomized, open-label trial evaluating fixed durations of epcoritamab in combination with R2 versus R2 alone in patients with relapsed or refractory FL. Efficacy was based on the dual primary endpoints of progression-free survival (PFS) and overall response rate (ORR), as assessed by an independent review committee (IRC). By intention-to-treat analysis (N=488), PFS was statistically significantly longer in the epcoritamab plus R2 arm, with a hazard ratio (HR) of 0.21 (95% CI: 0.13, 0.33) and p<0.0001 on first interim analysis. The median PFS was not reached (95% CI: 22, NR) in the epcoritamab plus R2 arm and was 11.2 months (95% CI: 10.5, NR) in the R2 arm. ORR per IRC was significantly higher in the epcoritamab plus R2 arm, based on prespecified analysis of the first 232 patients assessed (96% vs. 81% with R2;p<0.0001). This article summarizes key aspects of the regulatory review, including endpoint selection, randomized dose optimization, and a potential single-trial approach to support both accelerated and subsequent traditional approval.

A 2025 National Academies' report, The Science and Practice of Team Science, identified critical gaps in leadership development and highlighted evidence-based best practices and infrastructure needs to enhance team science. This brief perspective addresses team science approaches needed to overcome the complexities of cancer biology, carcinogenesis, and the processes for advancing cancer knowledge and clinical practice to effectively develop novel interventions. To define evidence-based leadership education programs rooted in the National Academies' report and tailored for cancer researchers, we conducted a survey-based educational needs assessment and performed a structured literature review using Medical Subject Headings terms for cancer and team science. The review identified 53 articles with few focused on team science leadership and none on team science leadership training for cancer research. Survey responses from 58 national cancer research leaders involved in NCI P30 CCSG (n=45), P01 (n=18), U54 (n=18), and P50 SPORE (n=16) programs identified key skills for successful team science leadership: team leadership, strategic planning, grant planning/writing, translational/clinical leadership, science communication, mentorship, and conflict resolution. Cancer research leaders identified the biggest gaps in current training as: team leadership, conflict resolution, team evaluation/metrics, systems thinking and analysis, and institutional navigation. From 68 mid-career faculty representing the audience for training, self-assessments revealed developing/managing large research grants, managing shared resources, and interdependencies as the most desired topics for training with most preferring training in‑person. Delivering structured training in the competencies of team science will better prepare established, independent investigators to lead larger complex, multi-component cancer research programs.

Precision oncology seeks to transform cancer treatment into one tailored for individual patients. Genomic alterations have been the dominant drivers of patient-specific therapeutic strategies. While genomic insights can guide treatment planning, genotype-directed therapies do not guarantee response to therapy. Functional confirmation of target expression, target engagement, and downstream biological effects is essential to defining therapeutic endpoints. Translational imaging can play a central role in closing the loop between genome and function to operationalize functional precision medicine (FPM). Quantitative co-clinical imaging provides a powerful framework to link genotype with function by confirming drug delivery, target engagement, pharmacodynamic effects, tumor function and heterogeneity across animal models and patients to advance FPM. Over the past decade, the Co-Clinical Imaging Research Resource Program (CIRP) of the National Cancer Institute (NCI) has made considerable progress in advancing quantitative imaging biomarker development. However, critical gaps remain in the integration and standardization of co-clinical imaging biomarkers. The next frontier requires moving beyond quantitative endpoints toward predictive oncology. This includes validating imaging-aware models, developing quantitative imaging strategies to support new precision medicine trials, and embedding co-clinical data into computational and in silico frameworks such as radiomics, cross-species mathematical modeling, digital twins, and virtual imaging trials. Equally important is the development of a domain-specific repository that vertically integrates imaging with multi-modal data to enable reproducible, artificial intelligence-ready pipelines. These advances will accelerate the translation of co-clinical imaging biomarkers into decision models that complement genomics, improve patient stratification, and guide selection and personalization of therapies-advancing the promise of FPM.