Cancer Biology

Internalisation of integrin-bound extracellular matrix modulates invasive carcinoma cell migration

1. Montserrat Llanses Martinez
2. Keqian Nan
3. Zhe Bao
4. Rachele Bacchetti
5. Shengnan Yuan
6. Joe Tyler
7. Xavier Le Guezennec
8. Frédéric A. Bard
9. Elena Rainero

Reviewed by Review Commons

Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model

1. Han V. Han
2. Richard Efem
3. Barbara Rosati
4. Kevin Lu
5. Sara Maimouni
6. Ya-Ping Jiang
7. Valeria Montoya
8. Adrianus W. M. Van Der Velden
9. Wei-Xing Zong
10. Richard Z. Lin

• Curated by eLife

  eLife assessment

  The significance of the findings is valuable, with implications for immunotherapy design in pancreatic ductal adenocarcinoma. The evidence was considered incomplete and partially supportive of the major claims.

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 M. M. 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. Steven F. Bellon

• Curated by eLife

  eLife assessment

  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. This study provides 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.

Reviewed by eLife

Ribosome subunit attrition and activation of the p53–MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition

1. Gregory Caleb Howard
2. Jing Wang
3. Kristie L Rose
4. Camden Jones
5. Purvi Patel
6. Tina Tsui
7. Andrea C Florian
8. Logan Vlach
9. Shelly L Lorey
10. Brian C Grieb
11. Brianna N Smith
12. Macey J Slota
13. Elizabeth M Reynolds
14. Soumita Goswami
15. Michael R Savona
16. Frank M Mason
17. Taekyu Lee
18. Stephen Fesik
19. Qi Liu
20. William P Tansey

• Curated by eLife

  eLife assessment

  This important paper reveals that one of the major roles of the WDR5 WIN site is to promote ribosome synthesis, and that by attacking the WIN site with inhibitors ribosome attrition occurs creating new vulnerabilities that can be therapeutically exploited. This deficiency of ribosomal proteins also provokes the p53 response. The data from a variety of approaches is generally very convincing, and together buttresses the authors' conclusions and interpretations quite nicely; overall, this paper will provide a justification for pre-clinical and translational studies of WDR5 interaction site inhibitors.

Reviewed by eLife

Multi-omic dataset of patient-derived tumor organoids of neuroendocrine neoplasms

1. Nicolas Alcala
2. Catherine Voegele
3. Lise Mangiante
4. Alexandra Sexton-Oates
5. Hans Clevers
6. Lynnette Fernandez-Cuesta
7. Talya L. Dayton
8. Matthieu Foll

Reviewed by GigaScience

DUX4 is a common driver of immune evasion and immunotherapy failure in metastatic cancers

1. Jose Mario Bello Pineda
2. Robert K Bradley

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the association between DUX4 expression with features of immune evasion in human tissue and clinical outcomes in patients with advanced urothelial cancer. The evidence supporting the claims of the authors is convincing, using a range of corroborative statistical techniques. Compared to an earlier version, the quality of the manuscript has been enhanced, for example Figure 5 now illustrates the key features of survival probability estimates over time for patients assigned to with the test or training set.

Reviewed by eLife

mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming

1. Helmut Bischof
2. Selina Maier
3. Piotr Koprowski
4. Bogusz Kulawiak
5. Sandra Burgstaller
6. Joanna Jasińska
7. Kristian Serafimov
8. Monika Zochowska
9. Dominic Gross
10. Werner Schroth
11. Lucas Matt
12. David Arturo Juarez Lopez
13. Ying Zhang
14. Irina Bonzheim
15. Florian A Büttner
16. Falko Fend
17. Matthias Schwab
18. Andreas L Birkenfeld
19. Roland Malli
20. Michael Lämmerhofer
21. Piotr Bednarczyk
22. Adam Szewczyk
23. Robert Lukowski

• Curated by eLife

  eLife assessment

  The large-conductance Ca2+ activated K+ channel BKCa has been reported to promote breast cancer progression. The present study presents convincing evidence that an intracellular subpopulation of this channel reprograms breast cancer cells towards the Warburg phenotype, one of the metabolic hallmarks of cancer. This important finding advances the field of cancer cell metabolism and has potential therapeutic implications.

Reviewed by eLife

DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation

1. Nicholas J Mullen
2. Surendra K Shukla
3. Ravi Thakur
4. Sai Sundeep Kollala
5. Dezhen Wang
6. Nina Chaika
7. Juan F Santana
8. William R Miklavcic
9. Drew A LaBreck
10. Jayapal Reddy Mallareddy
11. David H Price
12. Amarnath Natarajan
13. Kamiya Mehla
14. David B Sykes
15. Michael A Hollingsworth
16. Pankaj K Singh

• Curated by eLife

  eLife assessment

  This important study reports a novel mechanism linking DHODH inhibition and subsequent pyrimidine nucleotide depletion with upregulation of cell surface MHC I in cancer cells. The in vitro mechanistic data are compelling, with rigorous methodology and validation across multiple cell lines. The authors also provide in vivo evidence for additive effects of DHODH inhibitors and immune checkpoint blockade. However, the in vivo assessments of the functional relevance of this mechanism remain incomplete, requiring additional analyses to fully substantiate the conclusions made.

Reviewed by eLife

Single cell multi-omics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response

1. Rebecca Warfvinge
2. Linda Geironson Ulfsson
3. Parashar Dhapola
4. Fatemeh Safi
5. Mikael N.E. Sommarin
6. Shamit Soneji
7. Henrik Hjorth-Hansen
8. Satu Mustjoki
9. Johan Richter
10. Ram Krishna Thakur
11. Göran Karlsson

• Curated by eLife

  eLife assessment

  This study presents fundamental insights into the heterogeneity of chronic myeloid leukemia (CML) stem cells and their response to tyrosine kinase inhibitor therapy, shedding light on potential mechanisms underlying treatment failure. The study's robust methodology, supported by validation with bulk RNA-seq data and surface marker analysis, provides compelling evidence for the identified associations between cellular composition and treatment outcome. These findings contribute to our understanding of CML pathogenesis and may inform the development of more targeted therapeutic strategies.

Reviewed by eLife

SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells

1. Linda Zhang
2. Joanne I Hsu
3. Etienne D Braekeleer
4. Chun-Wei Chen
5. Tajhal D Patel
6. Alejandra G Martell
7. Anna G Guzman
8. Katharina Wohlan
9. Sarah M Waldvogel
10. Hidetaka Uryu
11. Ayala Tovy
12. Elsa Callen
13. Rebecca L Murdaugh
14. Rosemary Richard
15. Sandra Jansen
16. Lisenka Vissers
17. Bert BA de Vries
18. Andre Nussenzweig
19. Shixia Huang
20. Cristian Coarfa
21. Jamie Anastas
22. Koichi Takahashi
23. George Vassiliou
24. Margaret A Goodell

• Curated by eLife

  eLife assessment

  Gain-of-function mutations and amplifications of PPM1D are found across several human cancers and are associated with advanced tumor stage and worse prognosis. Thus far, the clinical translation has not been possible due to the lack of PPM1D inhibitors with favorable pharmacokinetic properties. This useful study leverages CRISPR/Cas9 screening to determine that loss of SOD1 and is synthetic lethal with PPM1D mutation in leukemia. The mechanistic analyses are still incomplete.

Reviewed by eLife