Cancer Biology

Design of combination therapeutics from protein response to drugs in ovarian cancer cells

1. Alexandra Franz
2. Ciyue Shen
3. Fabian Coscia
4. Kenneth Munroe
5. Lea Charaoui
6. Anil Korkut
7. Matthias Mann
8. Augustin Luna
9. Chris Sander

• Curated by eLife

  eLife Assessment

  In this important study, the authors provide a simple yet elegant approach to identifying therapeutic targets that synergize to prevent therapeutic resistance in ovarian cancer using cell lines, data-independent acquisition proteomics, and bioinformatic analysis. The authors convincingly identify several combinations of pharmaceuticals that were able to overcome or prevent therapeutic resistance in culture models of ovarian cancer, a disease with an unmet diagnostic and therapeutic need. This work will be of interest to researchers focused on ovarian cancer.

Reviewed by eLife

Caveolin-1 regulates context-dependent signaling and survival in Ewing sarcoma

1. Dagan Segal
2. Xiaoyu Wang
3. Hanieh Mazloom-Farisbaf
4. Felix Y. Zhou
5. Divya Rajendran
6. Erin Butler
7. Bingying Chen
8. Bo-Jui Chang
9. Khushi Ahuja
10. Averi Perny
11. Kushal Bhatt
12. Dana Kim Reed
13. Diego H. Castrillon
14. Jeon Lee
15. Elise Jeffery
16. Lei Wang
17. Khai Nguyen
18. Noelle S. Williams
19. Stephen X. Skapek
20. Satwik Rajaram
21. Reto Fiolka
22. Khuloud Jaqaman
23. Gary Hon
24. James F. Amatruda
25. Gaudenz Danuser

Reviewed by Review Commons

HER2-driven mammary tumorigenesis enhances bioenergetics despite reductions in mitochondrial content

1. Sara M Frangos
2. Henver S Brunetta
3. Dongdong Wang
4. Maria Joy Therese Jabile
5. Leslie Jeffries
6. Grace Mencfeld
7. David WL Ma
8. William J Muller
9. Cezar M Khursigara
10. Kelsey H Fisher-Wellman
11. Jim Petrik
12. Gregory R Steinberg
13. Graham P Holloway

• Curated by eLife

  eLife Assessment

  This valuable study aims to determine mechanisms underlying breast cancer initiation and tumour progression. The manuscript includes a solid set of transcriptomic and proteomic datasets from tumour samples and examines mitochondrial function within the tumours. While the underlying mechanisms linking expression changes to functional effects remain speculative. This paper provides a resource for researchers working on breast cancer and/or HER2-driven bioenergetics changes.

Reviewed by eLife

Human Oncogene EWS::FLI1 Functions as a Pioneer Factor in Saccharomyces cerevisiae

1. Diego Velázquez
2. Cristina Molnar
3. Jose Reina
4. Jaume Mora
5. Cayetano Gonzalez

Reviewed by Review Commons

A Transcriptional Signature of Metabolic-Immune Conflict Fails to Provide Independent Prognostic or Predictive Value in Melanoma

1. Islam Asal

Reviewed by PREreview

Cross-Species Transcriptomic Integration Reveals a Conserved, MIRO1-Mediated Macrophage-to-T Cell Signaling Axis Driving Immunosuppression in Glioma

1. Zehui Du
2. Menghan Li
3. Brandon H. Bergsneider
4. Andy P. Tsai
5. Kwang Bog Cho
6. Lily H. Kim
7. John Choi
8. Gordon Li
9. Tony Wyss-Coray
10. Michael Lim
11. Xinnan Wang

Reviewed by Review Commons

Blocking SHP2 benefits FGFR2 inhibitor and overcomes its resistance in FGFR2-amplified gastric cancer

1. Yue Zhang
2. Hanbing Wang
3. Yutao Wei
4. Yunfeng Pan
5. Xueru Song
6. Jie Shao
7. Lixia Yu
8. Tao Shi
9. Yue Wang

• Curated by eLife

  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.

Reviewed by eLife

Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics

1. David Papadopoli
2. Ranveer Palia
3. Predrag Jovanovic
4. Sébastien Tabariès
5. Emma Ciccolini
6. Valerie Sabourin
7. Sebastian Igelmann
8. Shannon McLaughlan
9. Lesley Zhan
10. HaEun Kim
11. Nabila Chekkal
12. Krzysztof J Szkop
13. Thierry Bertomeu
14. Jibin Zeng
15. Julia Vassalakis
16. Farzaneh Afzali
17. Slim Mzoughi
18. Ernesto Guccione
19. Mike Tyers
20. Daina Avizonis
21. Ola Larsson
22. Lynne-Marie Postovit
23. Sergej Djuranovic
24. Josie Ursini-Siegel
25. Peter M Siegel
26. Michael Pollak
27. Ivan Topisirovic

• Curated by eLife

  eLife Assessment

  The authors present an important set of data implicating ETFDH as an epigenetically suppressed gene in cancer with tumor suppressive functions. The evidence is convincing, with the authors demonstrating that suppression of ETFDH activity results in accumulation of amino acids that impact metabolism via hyperactive mTORC1.

Reviewed by eLife

The DBD-α4 helix of EWSR1::FLI1 is required for GGAA microsatellite binding that underlies genome regulation in Ewing sarcoma

1. Ariunaa Bayanjargal
2. Cenny Taslim
3. Iftekhar A Showpnil
4. Julia Selich-Anderson
5. Jesse C Crow
6. Runwei Zhou
7. Stephen L Lessnick
8. Emily R Theisen

• Curated by eLife

  eLife Assessment

  This paper investigates the Achilles' heel of an aggressive pediatric bone cancer known as Ewing sarcoma. The authors aimed to better understand how its previously undruggable drivers mediate oncogenic mechanisms using several omics approaches. Transcriptomic changes aligned with their findings provide convincing 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 new insights into the underlying oncogenic mechanisms in Ewing sarcoma.

Reviewed by eLife

Depletion of rRNA Methyltranferase METTL5 Enhances Anti-Tumor Immune Response via Neoantigen Generated from Cryptic Translation

1. Yangyi Zhang
2. Xiaoyan Shi
3. Yuci Wang
4. Ruiqi Wang
5. Folan Lin
6. Yanlan Cao
7. Wanqiu Li
8. Hao Chen

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding that depletion of the rRNA methyltransferase METTL5 enhances anti-tumor immunity through a novel mechanism involving neoantigen generation from non-canonical translation. The evidence supporting the central conclusions is solid, with comprehensive multi-omics data including ribosome profiling, immunopeptidomics, TCR sequencing, and multiple in vivo tumor models demonstrating synergy with immune checkpoint blockade.

Reviewed by eLife