Cancer Biology

Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition

1. Laleh S Arabanian
2. Jenni Adamsson
3. Anke Unger
4. Raffaella Di Lucrezia
5. Tim Bergbrede
6. Arghavan Ashouri
7. Erik Larsson
8. Peter Nussbaumer
9. Bert M Klebl
10. Lars Palmqvist
11. Claes M Gustafsson

• Curated by eLife

  eLife Assessment

  This solid study assesses a mitochondrial polymerase inhibitor in combination with the BCL-2 inhibitor venetoclax, with the aim to increase the elimination of acute myeloid leukemia. It provides valuable findings of combinatorial efficacy using preclinical models in vitro and in vivo, confirming the overall importance of targeting oxidative phosphorylation to overcome venetoclax resistance in acute myeloid leukemia, and could be strengthened through mechanistic studies demonstrating on target effects and pharmacodynamic efficacy in vivo. The study is of interest to hematologists because it addresses a key biomedical issue in acute myeloid leukemia (venetoclax resistance) and provides data regarding the safety and activity of a novel inhibitor of the mitochondrial polymerase in combination with venetoclax.

Reviewed by eLife

NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer

1. Shengsheng Zhao
2. Ji Lin
3. Bingzi Zhu
4. Yin Jin
5. Qiantong Dong
6. Xiaojiao Ruan
7. Dan Jin
8. Yongdong Yi
9. Binglong Bai
10. Hongzheng Li
11. Danna Liang
12. Jianhua Lu
13. Letian Meng
14. Xiang Wang
15. Yuekai Cui
16. Yuyang Gu
17. Xian Shen
18. Xufeng Lu
19. Shangrui Rao
20. Weijian Sun

• Curated by eLife

  eLife Assessment

  This fundamental study identified a novel role of NOLC1 in regulating p53 nuclear transcriptional activity and p53-mediated ferroptosis in gastric cancer. After major revisions, the evidence supporting the conclusions is solid. However, some new experiments are needed to draw more robust conclusions regarding the ferroptosis-associated studies.

Reviewed by eLife

Subtype-specific enhancer RNAs define transcriptional regulators and prognosis in breast cancers

1. Aamena Y Patel
2. Peyman Zarrineh
3. Jigar H Sheth
4. Sumitra Mohan
5. Mudassar Iqbal
6. Sankari Nagarajan

Reviewed by Review Commons

Drug-Induced p53 Activation Limits Pancreatic Cancer Initiation

1. Jennifer J Twardowski
2. Thomas I Heist
3. Zamira Guerra Soares
4. Emily S Berry
5. Luis I Ruffolo
6. Christoph Pröschel
7. Stephano S Mello

Reviewed by Review Commons

Single-cell dissection of prognostic architecture and immunotherap response in Helicobacter pylori infection-associated gastric cancer

1. Xin Zhang
2. Guangyu Zhang
3. Shuli Sang
4. Yang Fei
5. Xiaopeng Cao
6. Wenge Song
7. Feide Liu
8. Jinze Che
9. Haoxia Tao
10. Hongwei Wang
11. Lihua Zhang
12. Yiyan Guan
13. Shipeng Rong
14. Lijuan Pei
15. Sheng Yao
16. Yanchun Wang
17. Min Zhang
18. Chunjie Liu

• Curated by eLife

  eLife Assessment

  This study presents a valuable description of the cellular and transcriptional landscape of the tumor microenvironment in 27 gastric cancer (GC) patients based on their H. pylori status (HpGC, ex-HpGC, non-HpGC). The single-cell RNA sequencing dataset and computational analysis are convincing and provide a starting point that is of value for understanding H pylori-associated GC cell type composition, cell transitions, and mechanisms of response to therapy. The section correlating immunotherapy outcomes with GC cell type compositions from bulk RNAseq would have been strengthened by further comparing H. pylori GC versus non H. pylori GC.

Reviewed by eLife

Phosphodiesterase 1A physically interacts with YTHDF2 and reinforces the progression of non-small cell lung cancer

1. Chong Zhang
2. Zuoyan Zhang
3. Yueyi Wu
4. Yuchen Wu
5. Jing Cheng
6. Kaizhi Luo
7. Zhidi Li
8. Manman Zhang
9. Jian Wang
10. Xuesen Zhang
11. Yangling Li

• Curated by eLife

  eLife Assessment

  This manuscript provides valuable mechanistic insight into NSCLC progression, both in terms of tumour metastasis and the development of chemoresistance. The authors draw upon a range of techniques and assays and the evidence shown is solid and has been strengthened by incorporation of suggestions by the two reviewers. The work presented will be of interest to cancer biologists and more broadly to those interested in NSCLC translational studies.

Reviewed by eLife

Single-Cell Atlas of AML Reveals Age-Related Gene Regulatory Networks in t(8;21) AML

1. Jessica Whittle
2. Stefan Meyer
3. Georges Lacaud
4. Syed Murtuza Baker
5. Mudassar Iqbal

• Curated by eLife

  eLife Assessment

  This manuscript provides a single-cell transcriptomic atlas for AML (222 samples comprising 748,679 cells) integrating data from multiple studies. They use this dataset to investigate t(8;21) AML, and they reconstruct the Gene Regulatory Network and enhancer Gene Regulatory Network, which allowed identification of interesting targets. This aggregation is useful and can help infer differences in genetic regulatory modules based on the age of disease onset, which may help explain age-related variations in prognosis and disease development. However, result interpretations and the motivation and critical analysis of the applied computational methods are incomplete, and the statistical analyses lack control experiments and should be improved to avoid potential selection bias in the later analyses.

Reviewed by eLife

TopBP1 biomolecular condensates: a new therapeutic target in advanced-stage colorectal cancer

1. Laura Morano
2. Nadia Vezzio-Vié
3. Adam Aissanou
4. Tom Egger
5. Antoine Aze
6. Solène Fiachetti
7. Benoît Bordignon
8. Cédric Hassen-Khodja
9. Hervé Seitz
10. Louis-Antoine Milazzo
11. Véronique Garambois
12. Laurent Chaloin
13. Nathalie Bonnefoy
14. Céline Gongora
15. Angelos Constantinou
16. Jihane Basbous

• Curated by eLife

  eLife Assessment

  This valuable study demonstrates that the GSK-3 inhibitor AZD2858 inhibits the formation of TOPBP1 condensates and hence DNA damage responses in colorectal cancer cells. The evidence supporting the claims of the authors is convincing, although uncovering how this drug blocks bio-condensate formation would have strengthened the study. The work will be of interest to cancer researchers searching for synergistic drug combination strategies.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife

Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells

1. Yu-Chia Chen
2. Mamoru Takada
3. Aerica Nagornyuk
4. Muhan Yu
5. Hideyuki Yamada
6. Takeshi Nagashima
7. Masayuki Ohtsuka
8. Jennifer G DeLuca
9. Steven M Markus
10. Motoki Takaku
11. Aussie Suzuki

• Curated by eLife

  eLife Assessment

  This study provides valuable findings that MK2 inhibitor CMPD1 can inhibit the growth, migration and invasion of breast cancer cells both in vitro and in vivo. The evidence supporting the claims of the authors is solid, although the detailed molecular mechanism and additional animal experiments would strengthen the paper. This study will be of interest to the breast cancer field.

Reviewed by eLife

Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis

1. Xuantong Gong
2. Lishuang Gu
3. Di Yang
4. Yu He
5. Qian Li
6. Hao Qin
7. Yong Wang

• Curated by eLife

  eLife Assessment

  This study presents a useful finding for the ferroptosis-mediated tumor microenvironment (TME) in triple-negative breast cancer (TNBC) using public single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for functional studies of TME in TNBC. The work will be of interest to medical biologists working in the field of TNBC.

Reviewed by eLife