Cancer Biology

Transcriptional Subtypes on Immune Microenvironment and Predicting Postoperative Recurrence and Metastasis in Pheochromocytoma and Paraganglioma

1. Yang Liu
2. Xu Yan
3. Yibo Zhang
4. Zhenfu Gao
5. Fengrui Nan
6. Siyu Shi
7. Jingyun Chen
8. Lingyu Li

• Curated by eLife

  eLife Assessment

  This is a useful study, describing transcriptome-based PPGL subtypes and exploring the mutations, immune correlates, and disease progression of cases in each subtype. The cohort is a reasonable size, and a second cohort is included from TCGA. One of the key premises of the study is that identification of driver mutations in PPGL is incomplete and that compromises characterisation for prognostic purposes. This is a reasonable starting point on which to base characterisation using different methods.

Reviewed by eLife

Pharmacologic inhibition of BAF chromatin remodeling complexes as a therapeutic approach to transcription factor-dependent cancers

1. Richard C Centore
2. Luis MM Soares
3. Salih Topal
4. Rishi G Vaswani
5. Kana Ichikawa
6. Zhifang Li
7. Hong Fan
8. Jeremy W Setser
9. David L Lahr
10. Laura E Zawadzke
11. Xueying Chen
12. Kimberly D Barnash
13. Jordana Muwanguzi
14. Neville Anthony
15. Gabriel J Sandoval
16. Katharine Feldman
17. GiNell Elliott
18. Ammar Adam
19. David Huang
20. Yunji Davenport
21. Shawn Schiller
22. Kevin J Wilson
23. Johannes Voigt
24. Lan Xu
25. Martin Hentemann
26. David S Millan
27. Ho Man Chan
28. Carl P Decicco
29. Ryan G Kruger
30. Gromoslaw A Smolen
31. Steven F Bellon

• Curated by eLife

  eLife Assessment

  This study constitutes 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. 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.

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 important and can help infer differences in genetic regulatory modules based on the age of disease onset. Their compelling effort may help explain age-related variations in prognosis and disease development in subtype-specific manner.

Reviewed by eLife

Idiosyncratic and generic single nuclei and spatial transcriptional patterns in papillary and anaplastic thyroid cancers

1. Adrien Tourneur
2. Joel Rodrigues Vitória
3. Manuel Saiselet
4. Ligia Craciun
5. Denis Larsimont
6. Anne Lefort
7. Frederick Libert
8. Carine Maenhaut
9. Sabine Costagliola
10. Maxime Tarabichi
11. Mirian Romitti
12. Vincent Detours

Reviewed by Review Commons

Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer

1. Jessica Armand
2. Sungsoo Kim
3. Kibum Kim
4. Eugene Son
5. Minah Kim
6. Kevin Kalinsky
7. Hee Won Yang

• Curated by eLife

  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.

Reviewed by eLife

PTEN restrains SHH medulloblastma growth through cell autonomous and nonautonomous mechanisms

1. Zhimin Lao
2. Salsabiel El Nagar
3. Yinwen Liang
4. Daniel N Stephen
5. Alexandra L Joyner

• Curated by eLife

  eLife Assessment

  This valuable study provides insights into the role of Pten mutations in SHH-medulloblastoma, by using mouse models to resolve the effects of heterozygous vs homozygous mutations on proliferation and cell death throughout tumorigenesis. The experiments presented are convincing, with rigorous quantifications and orthogonal experimentation provided throughout, and the models employing sporadic oncogene induction, rather than EGL-wide genetic modifications, represent an advancement in experimental design. However, the study remains limited, such that the biological conclusions do not extend greatly from those in the extant literature. This could be addressed with additional experimentation focused on cell cycle kinetic changes at early stages, as well as greater characterization of macrophage phenotypes (e.g., microglia vs circulating monocytes). The work will be of interest to medical biologists studying general cancer mechanisms, as the function of Pten may be similar across tumor types.

Reviewed by eLife

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

1. Kevin Leguay
2. Omaima Naffati
3. Yu Yan He
4. Mireille Rogue
5. Chloe Tesniere
6. Melania Gombos
7. Hellen Kuasne
8. Louis Gaboury
9. Christian Le Gouill
10. Sylvain Meloche
11. Michel Bouvier
12. Sebastien Carreno

Reviewed by Review Commons

Multi-gradient Permutation Survival Analysis Identifies Mitosis and Immune Signatures Steadily Associated with Cancer Patient Prognosis

1. Xinlei Cai
2. Yi Ye
3. Xiaoping Liu
4. Zhaoyuan Fang
5. Luonan Chen
6. Fei Li
7. Hongbin Ji

• Curated by eLife

  eLife Assessment

  This paper contains valuable ideas for methodology concerned with the identification of genes associated with disease prognosis in a broad range of cancers. However, there are concerns that the statistical properties of MEMORY are incompletely investigated and described. Further, more precise details about the implementation of the method would increase the replicability of the findings by other researchers.

Reviewed by eLife

Human RAP2A Homolog of the Drosophila Asymmetric Cell Division Regulator Rap2l Targets the Stemness of Glioblastoma Stem Cells

1. Maribel Franco
2. Ricardo Gargini
3. Víctor M Barberá
4. Daniel Becerra
5. Miguel Saceda
6. Ana Carmena

• Curated by eLife

  eLife Assessment

  This useful study explores the role of RAP2A in asymmetric cell division (ACD) regulation in glioblastoma stem cells (GSCs), drawing parallels to Drosophila ACD mechanisms and proposing that an imbalance toward symmetric divisions drives tumor progression. While findings on RAP2A's role in GSC expansion are promising, and the reviewers found the study innovative and technically solid, the study relies on neurosphere models without in vivo confirmation and will therefore need to be further validated in the future.

Reviewed by eLife

Mutational and Expression Profile of ZNF217, ZNF750, ZNF703 Zinc Finger Genes in Kenya Women diagnosed with Breast Cancer

1. Michael Kitoi
2. John Gitau
3. Godfrey Wagutu
4. Kennedy Mwangi
5. Florence Ngonga
6. Francis Makokha

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on mutations in ZNF217, ZNF703, and ZNF750 through 23 breast cancer samples alongside matched normal tissues in Kenyan breast cancer patients. The evidence supporting the claims of the authors is solid, yet the analysis of the manuscript lacks methodological transparency, statistical detail, and sufficient comparison with existing large-scale datasets. The work will be of interest to medical biologists and scientists working in the field of breast cancer.

Reviewed by eLife