Cancer Biology

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

Blocking Osteoprotegerin Reprograms Cancer Associated Fibroblast to Promotes Immune Infiltration into the Tumor Microenvironment

1. Yao Wang
2. Hara Apostolopoulou
3. Im Hong Sun
4. Arjan Bains
5. David Gibbs
6. Sui Huang
7. Tamara Alliston
8. Ajay Maker
9. Thea Tlsty
10. Vasilis Ntranos
11. James M Gardner
12. Anil Bhushan

• Curated by eLife

  eLife Assessment

  This study presents an important finding by identifying OPG as a novel stromal checkpoint influencing T-cell anti-tumor responses, thereby shedding new light on the complex interplay between the tumor microenvironment and immune regulation. The data are robust and the experimental approaches are sound, providing solid support for the study's conclusions; however, there are a number of additional questions raised by the data. Of particular note are the questions raised on the mechanistic effects of TRAIL versus RANKL. In addition, it would broaden the interest in this study to include more translational human data to complement the work presented.

Reviewed by eLife

Degradation of LMO2 in T cell leukaemia results in collateral breakdown of transcription complex partners and causes LMO2-dependent apoptosis

1. Naphannop Sereesongsaeng
2. Carole Bataille
3. Angela Russell
4. Nicolas Bery
5. Fernando J Sialana
6. Jyoti Choudhary
7. Ami Miller
8. Terence Rabbitts

• Curated by eLife

  eLife Assessment

  This important paper reports the development of proteins and small molecules that induce degradation of a clinically-relevant oncogenic transcription factor, LMO2. The findings provide a proof of concept that PROTAC-type chemicals can be developed against intrinsically disordered proteins. The methods provide a blueprint for rational design of PROTACs starting from intracellular antibody paratopes. Overall, the paper is supported by solid evidence and will be of interest to chemical biologists and cancer pharmacologists.

Reviewed by eLife

Sex differences in bile acid homeostasis and excretion underlie the disparity in liver cancer incidence between males and females

1. Megan E Patton
2. Sherwin Kelekar
3. Lauren J Taylor
4. Angela E Dean
5. Qianying Zuo
6. Rhishikesh N Thakare
7. Sung Hwan Lee
8. Emily Gentry
9. Morgan Panitchpakdi
10. Pieter Dorrestein
11. Yazen Alnouti
12. Zeynep Madak-Erdogan
13. Ju-Seog Lee
14. Milton J Finegold
15. Sayeepriyadarshini Anakk

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the influence of sex on bile acid metabolism and the risk of hepatocellular carcinoma (HCC). The data to support that there are inter-relationships between sex, bile acids, and HCC in mice are convincing, although this is a largely descriptive study. Future studies are needed to understand the interaction of sex hormones, bile acids, and chronic liver diseases and cancer at a mechanistic level. Also, there is not enough evidence to determine the clinical significance of the findings given the differences in bile acid composition between mice and men.

Reviewed by eLife