Zhang et al. report a randomized phase 2 trial for diffuse large B cell lymphoma (DLBCL) that compared standard of care (R-CHOP) to R-CHOP combined with one of 5 agents matched to an individual lymphoma’s genetics. Overall, the matching strategy significantly outperformed R-CHOP, laying the foundation for a paradigm-shifting phase 3 trial.

Increasing evidence suggests that tumors harbor diverse microbiomes, adding complexity to the tumor microenvironment. In this issue of Cancer Cell, Liu et al. highlight the role of the intratumor mycobiome, specifically Aspergillus sydowii, in promoting lung adenocarcinoma progression. A. sydowii enhances the recruitment and activation of myeloid-derived suppressor cells via IL-1β signaling driven

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Successful implementation of adoptive cell therapy (ACT) of cancer requires comprehensively addressing biological and practical challenges. This approach has been largely overlooked, resulting in a gap between the potential of ACT and its actual effectiveness. We summarize the most promising technical strategies in creating an “ideal” ACT product, focusing on chimeric antigen receptor (CAR)-engineered

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.

In this issue of Cancer Cell, Topp et al. analyze data from 799 patients treated with pembrolizumab beyond progression by RECIST 1.1 across six trials. Although 8.9%–24.4% of patients demonstrate a ≥30% reduction in target lesions, conversely 11%–18% of patients had a ≥20% increase. The benefits of treatment beyond progression must be carefully weighed against physical and financial toxicities.

The CD58-CD2 axis regulates T cell-mediated cancer immunity, but little is known about the regulation of CD58. In two recent papers pubished in Cancer Cell, Miao et al. and Ho et al. define a mechanism of CD58 regulation by CMTM6 and show an unexpected yin-yang link between PD-L1 and CD58.

Brain metastases cause cognitive impairment and impair quality of life. Sanchez-Aguilera et al. examine the effects of metastases on brain function leveraging in vivo electrocorticography and machine learning to reveal tumor model-specific changes in neural circuit dynamics and find that the electrophysiological profile predicts the presence and type of brain metastasis.

Artificial intelligence (AI) is rapidly gaining interest in medicine, including pathological assessments for personalized medicine. In this issue of Cancer Cell, Wagner et al. demonstrate superior accuracy of transformer-based deep learning in predicting biomarker status in CRC. The work has implications for increased efficiency and accuracy in clinical diagnostics guiding treatment decisions in precision

Among new treatment approaches for patients with cancer, few have accelerated as quickly as neoadjuvant immune checkpoint blockade (ICB). Neoadjuvant cancer therapy is administered before curative-intent surgery in treatment-naïve patients. Conventional neoadjuvant chemotherapy and radiotherapy are primarily intended to reduce tumor size, improving surgical resectability. However, recent scientific

By integrating scRNA-seq datasets across 77 studies and 24 cancer types, in Nature, Gavish et al. uncover recurrent patterns of gene expression that explain a significant proportion of transcriptomic heterogeneity observed in cancer and explore their functional significance.

The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 tumors in 10 cohorts to create a cohesive

The exact mechanisms that govern clonal dynamics and selection during early tumorigenesis remain largely elusive. Ceresa et al. provide experimental and mathematical evidence that MYC-dependent competition between individual clones is one driving force of brain tumor evolution, adding a winner/loser aspect to the picture that complements existing concepts.

Chromophobe renal cell carcinoma (ChRCC) is the second most common variant histology RCC. ChRCC is distinct from clear cell RCC (ccRCC) in terms of genetics, genomics, metabolism, cell of origin, and response to targeted and immune therapies. The pathogenesis of ChRCC remains unclear, but current data suggest two potential mechanisms: mTORC1 hyperactivation through PTEN pathway mutations and mitochondrial

The role of gut microbiota and their sex-specific differences in colorectal cancer remain to be explored. In the current issue of Cancer Cell, Li et al. discovered that estrogen facilitates the colonization of Carnobacterium maltaromaticum in the mouse gut and exerts its anti-colorectal cancer effects by increasing the production of vitamin D3.

Studies have established immunochemotherapy as the first-line treatment for advanced esophageal cancer. Chen et al. and Carrol et al. performed exploratory analysis of the JUPITER-06 and LUD2015-005 trials, respectively and identified biomarkers to predict therapy response based on immunogenomic analysis. These findings may optimize precise patient stratification in advanced esophageal cancer.

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The genetic changes during high-grade serous ovarian cancer metastasis have largely remained a mystery. Lahtinen et al. show that ovarian cancer metastasizes along three different evolutionary states that have distinct mutations and signaling pathways, potentially allowing the identification of targeted treatments.

Taxanes are widely used in cancer therapy, yet their mitotic-independent mechanisms in vivo remain enigmatic. Vennin et al. illuminate a mode of action whereby taxanes directly stimulate T cells to release cytotoxic extracellular vesicles to eradicate tumor cells. Taxanes-pre-treated T cells may enhance anti-tumor effects while circumventing systemic toxicity.

Abstract not available

Senescent cells accumulate following oncogene induction, but their role in transformation remains unclear. Prieto et al. and Haston et al. found that senescent cells in premalignant lung lesions are mainly macrophages that promote lung tumorigenesis, and removing them through senolytic approaches can prevent malignant progression.

Cholesterol is essential for the ability of cytotoxic T cells to eliminate cancer cells. In this issue of Cancer Cell, Yan et al. reveal how intra-tumoral cholesterol deficiency contributes to T cell exhaustion by inhibiting mTORC1 signaling. Moreover, they demonstrate that increasing cholesterol levels in chimeric antigen receptor (CAR)-T cells by blocking liver X receptor (LXR) leads to improved