The paper details the development and application of DBiTplus, an advanced multi-omics platform designed for spatial transcriptomic and proteomic mapping within the same tissue section. This methodology improves upon previous techniques by using microfluidic barcoding and thermostable RNase H to achieve high-quality cDNA recovery while maintaining tissue integrity. Researchers successfully applied this tool to mouse embryos and human lymphoma tissues, enabling the identification of distinct cellular clusters that correspond to specific anatomical regions. By integrating multiplexed immunofluorescence with gene expression data, the study reveals complex biological transitions, such as the transformation of chronic lymphocytic leukemia into more aggressive diffuse large B-cell lymphoma. The findings demonstrate how spatial gradients of immune exhaustion and metabolic reprogramming drive tumor progression. Ultimately, this high-resolution approach provides a robust framework for investigating the molecular architecture of both healthy development and disease states.

References:

• Enninful A, Zhang Z, Klymyshyn D, et al. Integration of imaging-based and sequencing-based spatial omics mapping on the same tissue section via DBiTplus[J]. Nature Methods, 2026: 1-13.

This research integrates multiomic data to identify a specific, high-risk subtype of Group 3 medulloblastoma characterized by a unique lipid dependency. By analyzing proteomic and metabolic signatures, the authors discovered that MYC-driven tumors rely on the accumulation of lipid droplets to fuel mitochondrial activity and promote cell survival. This metabolic reprogramming creates a targetable vulnerability where the enzyme DGAT1 plays a critical role in managing lipid homeostasis. Experimental evidence demonstrates that inhibiting DGAT1 reduces tumor growth and enhances the effectiveness of chemotherapy in preclinical models. Ultimately, the study provides a molecular framework for developing new therapeutic strategies against these aggressive and lethal childhood brain tumors.

References:

• Bernardi F, Torrejon J, Basili I, et al. Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma[J]. Cancer Cell, 2026.

The ADAPT initiative, launched by ARPA-H, aims to modernize oncology by shifting from static treatments to a dynamic, evolution-based care model. This national program utilizes interpretable artificial intelligence and multimodal data to predict how tumors will change and develop resistance in near real time. By integrating longitudinal biomarkers with an innovative evolutionary clinical trial framework, the system allows doctors to adjust therapies as a patient’s cancer mutates. A centralized Treatment and Analysis Platform facilitates the rapid sharing of clinical insights across institutions to ensure treatments remain ahead of disease progression. Ultimately, the program seeks to improve survival rates for metastatic cancers by making precision medicine more responsive to the biological shifts of each tumor.

References:

• Bild A H, Sangar M C, McQuerry J A, et al. The ADAPT learning cancer treatment system: ARPA-H’s initiative to revolutionize cancer therapy[J]. Cancer Cell, 2026.

This research presents a comprehensive proteogenomic analysis of gallbladder cancer (GBC) to uncover the molecular drivers of its high mortality and clinical diversity. By integrating genomic, transcriptomic, and proteomic data, the authors identified four distinct molecular subtypes and four immune microenvironment profiles that correlate with patient prognosis and drug sensitivity. A key discovery involves the role of metabolic reprogramming, specifically through proteins like ACAT1 and PHGDH, in fueling the liver invasion that characterizes advanced disease. The study also explores the rare neuroendocrine variant of GBC, identifying the transcription factor MEIS1 as a critical regulator of cellular transdifferentiation. These findings establish a therapeutic framework aimed at personalizing treatment strategies, such as combining immunotherapy with metabolic or kinase inhibitors. Ultimately, the data provides a high-resolution map of the GBC landscape to assist in the development of targeted clinical interventions.

References:

• Fu Z, Song Y, Liu F, et al. Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer[J]. Cancer Cell, 2026.

This research article presents a multimodal single-cell atlas of diffuse large B cell lymphoma (DLBCL) to better understand the disease's molecular heterogeneity. By analyzing over 500,000 cells from 103 patient biopsies, the authors identified distinct gene expression signatures for established genetic subtypes and discovered that most tumors contain genetically diverse subclones. These subclones exhibit varying phenotypic themes related to cell growth, proliferation, and specific stages of B cell differentiation. The study highlights how specific genetic alterations, such as REL amplification, can block normal cell maturation, contributing to the cancer's aggressive nature. Furthermore, the researchers mapped transcription factor networks to show how these malignant cells hijack normal biological pathways. Ultimately, these findings offer a comprehensive resource for identifying biomarkers that may predict how patients will respond to chemotherapy and targeted treatments.

References:

• Axes of biological variation in diffuse large B cell lymphoma
• Wang, Boya et al.Cancer Cell, Volume 0, Issue 0

The ASCEND-CRC program is a pioneering initiative designed to address the limitations of static cancer treatments by tracking tumor evolution in real time. Rather than relying on a single initial biopsy, this framework utilizes longitudinal multimodal profiling of tissue and blood to identify how colorectal cancer adapts and develops resistance. By monitoring dynamic biomarkers and early stress responses, the program aims to shift oncology from a reactive model to a proactive one that intercepts resistance before it becomes untreatable. The study operates in two stages, starting with an observational phase to map evolutionary patterns followed by an interventional phase where therapies are adjusted based on a tumor's specific molecular changes. This approach seeks to provide personalized interventions that match the fluid nature of cancer, potentially improving survival rates for patients with metastatic disease. Through this scalable platform, researchers hope to establish a new standard for precision medicine that outpaces the speed of malignant adaptation.

References:

• Alonso S, Raghav K, Morris V K, et al. Framework for cancer evolution profiling and interception in colorectal cancer: ASCEND-CRC program[J]. Cancer Cell, 2026.

This research identifies ADAM12 as a critical molecular checkpoint in cancer-associated fibroblasts (CAFs) that actively prevents the immune system from attacking tumors. Using advanced CRISPR-based single-cell screening on patient tissues, scientists discovered that ADAM12 maintains a pro-tumor environment by fueling TGF-β signaling and suppressing beneficial interferon responses. When ADAM12 is removed, fibroblasts shift from a restrictive "cold" state to a progenitor-like state that permits CD8+ T cell infiltration. This cellular reprogramming successfully shrinks tumors and significantly boosts the effectiveness of immunotherapy in various preclinical models. Because ADAM12 is primarily found in tumors rather than healthy tissue, it represents a highly promising and precise therapeutic target for treating solid cancers.

References:

• Li J, Liu H, Guo Q, et al. Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity[J]. Cancer Cell, 2026.

This research study utilizes imaging mass cytometry to map the complex cellular landscape of triple-negative breast cancer and identify markers that predict success with immunotherapy. By analyzing nearly two million cells from patients in a randomized trial, scientists discovered that the spatial organization and proliferation of specific immune cells before treatment are primary indicators of a positive response. The study highlights how the multicellular structure of a tumor evolves during therapy, noting that high levels of proliferating T cells correlate with recovery. Conversely, the presence of CD15+ cancer cells and specific plasma cell interactions on-treatment often signal resistance to therapy. Ultimately, these findings suggest that examining the physical interactions between cancer and immune cells can significantly improve the precision of cancer treatments.

References:

• Wang, X.Q., Danenberg, E., Huang, CS. et al. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature 621, 868–876 (2023). doi.org

This research explores the molecular machinery that governs exocytic membrane fusion within cells, specifically focusing on the exocyst complex and its regulatory proteins. Scientists utilized advanced cryo-electron tomography and super-resolution microscopy to analyze how the exocyst interacts with SNARE proteins like Sec9 and Sec18 to facilitate vesicle transport. By engineering inducible depletion systems in yeast, the study examines the specific roles these proteins play in anchoring and fusing vesicles to the plasma membrane. The data includes AlphaFold3 predictions and quantitative imaging to map the physical organization and copy numbers of these protein assemblies. Ultimately, the work provides a high-resolution look at the kinetic mechanisms and structural transitions that drive vesicle secretion.

References:

• Puig-Tintó M, Ortiz S, Meek S, et al. Continuum architecture dynamics of vesicle tethering in exocytosis[J]. Cell, 2026.

The paper describes the development of supramolecular targeting chimeras (SupTACs), a modular platform designed for targeted protein degradation with high spatial and temporal precision. By utilizing self-assembling nanoparticles, this technology enables the selective elimination of disease-related proteins within specific organs like the liver and lungs. The researchers demonstrated the platform's versatility across multiple species, including mice, dogs, and non-human primates, to treat conditions such as acute lung injury. Furthermore, the use of chemically caged variants allows for on-demand activation of the degradation process through bioorthogonal chemistry. This innovation addresses the limitations of traditional therapies by providing a programmable and scalable approach to modulating protein functions in vivo. Overall, SupTACs represent a significant advancement in precision medicine and the study of complex biological signaling networks.

References:

• Liu J, Ma T, Yao R, et al. Multimodal supramolecular targeting chimeras enable spatiotemporally resolved protein degradation in vivo[J]. Cell, 2026.