Cancer Biology

eLife Assessment

This useful study uses the MMTV-Neu-YD5 mouse model for HER2-dependent breast cancer to generate transcriptomic and proteomic datasets from extracted primary tumour samples. The data sets generated appear to be solid and will be of interest to the community. However, mechanistic studies to support the conclusion that mitochondrial function is increased in the tumours remain incomplete and would benefit from experiments that would directly interrogate aspects such as cellular heterogeneity, and signalling.

eLife Assessment

This study provides compelling data regarding the molecular characterization of a rare tumor type with few treatment options. This fundamental work significantly advances our mechanistic understanding of solitary fibrous tumours, a critical first step towards targeted precision medicine approaches. The results of this study will be of broad interest to cancer biologists and experimental oncologists.

eLife Assessment

This study provides a valuable approach to image and analyze in vivo metabolic flux through glucose turnover kinetics in glioblastoma tumor microenvironments. The evidence for the method's validity is convincing, which establishes the dynamic Deuterium Metabolic Imaging technique as an effective tool enabling non-invasive exploration of various tumors.

eLife Assessment

This study presents a valuable finding that synthetically lethal kinase genes FYN and KDM4 may play a role in drug resistance to kinase inhibitors in TNBC. The evidence supporting the claims of the authors is solid, although the exploration of the upstream mechanisms regulating KDM4A or the downstream pathways through which FYN upregulation confers drug resistance would have strengthened the study. The work will be of interest to medical biologists working in the field of breast cancer.

eLife Assessment

This important study provides solid evidence to support the anti-tumor potential of citalopram, originally an anti-depression drug, in hepatocellular carcinoma (HCC). In addition to their previous report on directly targeting tumor cells via glucose transporter 1 (GLUT1), they tried to uncover additional working mechanisms of citalopram in HCC treatment in the current study. The data here suggested that citalopram may regulate the phagocytotic function of TAM via C5aR1 or CD8+T cell function to suppress HCC growth in vivo.

eLife Assessment

This valuable study investigated the role of PLECTIN, a cytoskeletal crosslinker protein, in hepatocellular carcinoma development and progression. Using a liver-specific Plectin knockout mouse model, the authors showed solid evidence that PLECTIN is critical for hepatocarcinogenesis, since inhibition of PLECTIN suppressed tumor formation in multiple models. They also show that PLECTIN is key for HCC invasion and metastasis. They show a correlation between PLECTIN inhibition and attenuated FAK, MAPK/ERK, and PI3K/AKT signaling.

eLife Assessment

This study presents fundamental insights into overcoming resistance in hormone receptor-positive breast cancer by demonstrating that sustained CDK4/6 inhibitor treatment, either alone or in combination with CDK2 inhibitors, significantly suppresses the growth of drug-resistant cancer cells. The findings are supported by compelling evidence from both in vitro cell line experiments and in vivo mouse models, highlighting the therapeutic potential of maintaining CDK4/6 inhibitors beyond disease progression. Additionally, the identification of cyclin E overexpression as a key driver of resistance offers a target that will be of value for future therapeutic strategies, potentially improving outcomes for patients with advanced breast cancer.

eLife Assessment

This manuscript provides an important overview of potential resistance mutations within MET Receptor Tyrosine Kinase. The evidence supporting the findings is convincing - it should be pointed out that the approach is comparatively new for the application of protein kinases and the results are therefore of potentially great value. The results will be of value for clinicians facing drug resistance mutations, computational biologists who are training models of drug resistance mechanisms and biologists with an interest in cell signaling.

eLife Assessment

The ingenious design in this study achieved the observation of 3D cell spheroids from an additional lateral view and gained more comprehensive information than the traditional one angle of imaging. This extended the methods to investigate cell behaviors in the growth or migration of tumor organoids in a time-lapse manner and these extensions should be important to the field. The authors provide compelling evidence that the methods work as described.

eLife Assessment

Based on the perceived low efficacy of current therapies targeted to FGFR2 in gastric cancer (GC), the authors investigate an approach which combines SHP2 inhibition with existing FGFR2 inhibitors. The data were largely collected and analysed using solid and validated methodology. There is some useful data regarding combination therapy in a new clinical cohort, which supports previous studies that have reported the potential of targeting RTKs together with phosphatases.