Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Sandén et al. report that the ligand signaling lymphocyte activation molecule family member 6 protects acute myeloid leukemia cancer cells from T cell-mediated killing, leading to immune escape, and show that this can be targeted by a blocking antibody.

Neri and colleagues discuss the development of drug conjugates for cancer therapy, focusing on current and future opportunities to improve tumor-targeting efficacy with small molecule–drug conjugates and combination therapies.

Ubellacker and Dixon summarize the latest discoveries on ferroptosis in cancer, covering the molecular and cellular pathways underlying sensitivity and resistance to this type of cell death, as well as potential translational applications in cancer therapeutics.

Majzner and colleagues show that engineering T cells with a membrane-tethered version of the signaling adaptor molecule SLP-76 alongside a chimeric antigen receptor (CAR) enhances CAR T cell activity against low-antigen-density tumors.

Qian and colleagues show that MEF2D⁺ cancer precursors reprogram liver-resident Kupffer cells to create a microenvironment supporting liver tumorigenesis.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Sandén et al. report that the ligand signaling lymphocyte activation molecule family member 6 protects acute myeloid leukemia cancer cells from T cell-mediated killing, leading to immune escape, and show that this can be targeted by a blocking antibody.

Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.

Shao et al. developed an MRI–pathology-based foundation model to assess the pathology of prostate cancer for diagnosis and grading of tumors. The model is noninvasive and outperforms current pathological assessments.

Investment continues as the field awaits phase 3 readouts for next-generation radioligand therapies in 2026.

Propelled by a growing understanding of nasopharyngeal carcinoma pathogenesis through elucidation of its genomic and immune landscape, therapy has progressed from radiotherapy alone to combined chemotherapy and immunotherapy. This Clinical Outlook focuses on recent milestones and future directions for patients with nasopharyngeal carcinoma.

Ron DePinho received his MD from the Albert Einstein College of Medicine and completed his medical and postdoctoral training at Columbia University. He was the founding director of the Belfer Center at the Dana-Farber Cancer Institute. As president of the University of Texas MD Anderson Cancer Center, he launched the Cancer Moonshot initiative. He currently serves as a professor of cancer biology at the MD Anderson Cancer Center and was elected to the National Academies of Sciences and Medicine. He is the co-founder of several biotech companies and an advocate for innovation-driven healthspan solutions for the underserved.