Cancer Biology

eLife assessment

The significance of the findings is valuable, with implications for immunotherapy design in pancreatic ductal adenocarcinoma. The evidence was considered incomplete and partially supportive of the major claims.

eLife assessment

This study presents a valuable finding on the mechanism to promote distant metastasis in breast cancer. The evidence supporting the claims of the authors is convincing. The work will be of interest to medical biologists working on breast cancer.

eLife assessment

This is valuable work showing that a combination of drugs can reduce growth of Diffuse midline gliomas (clinically classified as DMG, H3 K27M-mutant) when applied in vitro and in tumor xenografts in mice. It is a significant first step towards understanding how these drugs work, and provides convincing results to encourage future pre-clinical studies. Further rationale on how doses for specific drugs were chosen, directly demonstrating a survival benefit, or implicating the Pin1 pathway components mechanistically, would make the manuscript stronger.

eLife assessment

This study provides a useful strategy for treating mouse cutaneous squamous cell carcinoma (mCSCC) with serum derived from mCSCC-exposed mice. The exploration of serum-derived antibodies as a potential therapy for curing cancer is particularly promising but the study provides inadequate evidence for specific effects of mCSCC-binding serum antibodies. This study will be of interest to scientists seeking a novel immunotherapic strategy in cancer therapy.

eLife assessment

This work substantially advances our understanding of pharmacological inhibition of SWI/SNF as a therapeutic approach for cancer. The study is well-written and provides compelling evidence, including comprehensive datasets, compound screens, gene expression analysis, epigenetics, as well as animal studies. This study provides a fundamental advance for the uveal melanoma research field that might be exploited to target this deadly cancer and more generally for targeting transcriptional dependency in cancers.

eLife assessment

The study is useful by attempting to present a new approach of combining two measurements (pHLA binding and pHLA-TCR binding) in order to refine predictions of which patient mutations are likely presented to and recognized by the immune system, but the evidence is incomplete. Whereas the novel methodology proposed is compelling, this article lacks a detailed explanation of the chosen model. The experimental validation confirming the computational predictions with actual immune responses is limited due to sample constraints.

eLife assessment

This important study combines in vivo and in vitro models to characterise the role of CYRI-B, an interactor of the small GTPase Rac1, in controlling pancreatic cancer progression towards a higher proliferative and metastatic stage. The evidence supporting the claims of the authors is convincing in characterizing a novel Rac1 binding protein, CYRI-B, as a regulator of metastatic potential in vivo, with distinct functions at different stages of tumour progression. CYRI-B reduces the typical hyperactivation of Rac1 in the early stages of tumour progression; subsequently, CYRI-B mediates internalization of lysophosphatidic acid receptor 1 (LPAR1) uptake through macropinocytosis, thus regulating chemotactic migration of cancer cells towards lysophosphatidic acid (LPA). Although the inclusion of human pancreatic cancer cell lines would have strengthened the study, the work will be of broad interest to cell biologists and the signalling research communities.

eLife assessment

This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide a solid base of evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable insight into the underlying oncogenic mechanisms in Ewing sarcoma, but is limited to a single cell line and would benefit from consolidation of the main conclusions using additional techniques.

eLife assessment

The main finding in this paper is that EGFR can be a novel substrate of the membrane ZNRF3/RNF43 E3 ligases. This is significant as the prevailing understanding posits that the Wnt receptors Frizzled and LRP5/6 exclusively served as substrates for these ligases. Given the frequent occurrence of mutations in ZNRF3/RNF43 or compromised expression levels in human cancers, the new evidence that aberrant EGFR expression and signaling may also contribute to the tumorigenic effects of ZNRF3/RNF43 mutations in cancer is important. The conclusions of the manuscript are supported by solid data, but some aspects of the mechanism presented need to be reinforced to fully support the claims made by the authors.

eLife assessment

Sisigano et al. report findings about the role of sphingolipids using lipidomics with machine learning in paclitaxel-induced peripheral neuropathy and preliminary translation of the impact of SA1P in cultured neuronal cells. This study presents a valuable finding on the increased activity of two well-studied signal transduction pathways in a subtype of breast cancer. The strength of evidence is incomplete with some support for the main claims with some limitations.

eLife assessment

This study presents a valuable finding and developed ME3BP-7 as a novel microencapsulated form of 3BP targeting MCT1 overexpressing PDAC cells, demonstrating its specificity and efficacy in vitro and in PDAC mouse models with significant anti-tumor effects and improved serum stability. The evidence supporting the claims of the authors is solid; however, the study calls for additional comparative in vivo data to enhance its translational significance.

eLife assessment

This important work substantially advances our understanding of how resistant leukemia can arise without changes in mutational patterns by displaying epigenetic changes. The evidence supporting the conclusions is compelling, with rigorous genomic assays done on primary samples. and state-of-the-art microscopy. The work will be of broad interest to hematologists and cancer biologists.

eLife assessment

This valuable study provides the detailed molecular mechanism of how OGT, an O-GlcNac transferase, promotes cancer progression. Using loss-of-function OGT models, the authors demonstrated that OGT cleaves HCF-1, a guardian of genomic stability. These solid findings can lead to some potential approaches to modulate anti-tumor immunity by targeting this process.

eLife assessment

This study presents an important finding on the role of telomeres in modulating interleukin-1 signaling and tumor immunity in TNBC. The evidence supporting these findings is solid, presented through comprehensive analyses including TNBC clinical samples, tumor-derived organoids, cancer cells, and xenografts. The work will be of broad interest to cell and medical biologists focusing on TNBC.

eLife assessment

This study presents a valuable finding on the roles and mechanisms of FYN and KDM4 in TNBC tumor cell resistance. The evidence supporting the claims of the authors is somewhat incomplete and the refinement of certain experiments would have strengthened the study. Noteworthy, FYN has been implied in drug resistance previously and this should be carefully discussed in the manuscript. The work will be of interest to scientists working on breast cancer.

eLife assessment

This study presents an important finding on the splicing regulatory function of RBM7 and its functional impact in breast cancer metastasis. The evidence supporting the claims of the authors is solid, although the inclusion of more delineation of how RBM7 regulates NF-kB and coordinates splicing would have strengthened the study. The work will be of interest to scientists working on breast cancer.

eLife assessment

This useful study utilizes proteomics analysis across a large panel of 51 cancer cell lines to elucidate mechanisms underlying the sensitivity of cancer cells to high-dose vitamin C (Ascorbate). While the associations between specific molecular pathways and sensitivity to ascorbate are interesting, a major limitation is that the study is largely descriptive and incomplete, lacking evidence on the molecular underpinnings of cancer cells' sensitivity to high-dose vitamin C.

eLife assessment

The authors address the function of keratin 17 (K17), a marker of the most aggressive pancreatic ductal adenocarcinomas (PDACs). While this potentially useful study addresses a significant area of pancreatic cancer research, the lack of evidence demonstrating nuclear localization of K17 in human PDAC and the excessive reliance on a single cell line reduce the significance of the work. Moreover, the weak phenotypes of K17 phosphosite mutants provide incomplete support for the authors' mechanistic model.

eLife assessment

This study provides an important finding that the local abundance of metabolites impacts the biology of the tumor microenvironment by utilizing kidney tumors from patients and adjacent normal tissues. The evidence supporting the claims of the authors is convincing although certain caveats need to be taken into consideration as the authors acknowledged in the paper. The work will be of interest to the research community working on metabolism and on kidney cancer especially.