Cancer Biology

Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas

1. Anne Fajac
2. Iva Simeonova
3. Julia Leemput
4. Marc Gabriel
5. Aurélie Morin
6. Vincent Lejour
7. Annaïg Hamon
8. Jeanne Rakotopare
9. Wilhelm Vaysse-Zinkhöfer
10. Eliana Eldawra
11. Marina Pinskaya
12. Antonin Morillon
13. Jean-Christophe Bourdon
14. Boris Bardot
15. Franck Toledo

• Curated by eLife

  eLife assessment

  This important study using engineered mouse models provides a first and compelling demonstration of a pathogenic phenotype associated with lack of expression of p53AS, an isoform of the p53 protein with a different C-terminus than canonical p53. The role of this isoform has been elusive so far and this first demonstration represents a substantial advance in our understanding of the complex role(s) of p53 isoforms. The revised manuscript adequately addresses previous concerns.

Reviewed by eLife

BMP antagonist CHRDL2 enhances the cancer stem‐cell phenotype and increases chemotherapy resistance in colorectal cancer

1. Eloise Clarkson
2. Annabelle Lewis

Reviewed by Review Commons

Targeting ribosome biogenesis as a novel therapeutic approach to overcome EMT-related chemoresistance in breast cancer

1. Yi Ban
2. Yue Zou
3. Yingzhuo Liu
4. Sharrel Lee
5. Robert B Bednarczyk
6. Jianting Sheng
7. Yuliang Cao
8. Stephen TC Wong
9. Dingcheng Gao

• Curated by eLife

  eLife assessment

  This study presents a valuable finding that pathways associated with ribosome biogenesis (RiBi) are activated during transition cell states and targeting ribosome biogenesis could be a viable approach to overcome EMT-related chemoresistance in BCs. The evidence supporting the claims of the authors is quite solid, although inclusion of additional experimental support that blocking of EMT/MET is necessary for the synergistic effect of standard chemotherapy together with RiBi blockage would have strengthened the study. The work will be of interest to scientists working on breast cancer.

Reviewed by eLife

Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancer

1. Phaedra C Ghazi
2. Kayla T O'Toole
3. Sanjana Srinivas Boggaram
4. Michael T Scherzer
5. Mark R Silvis
6. Yun Zhang
7. Madhumita Bogdan
8. Bryan D Smith
9. Guillermina Lozano
10. Daniel L Flynn
11. Eric L Snyder
12. Conan G Kinsey
13. Martin McMahon

• Curated by eLife

  eLife assessment

  This is a mechanistic study showing the effect of combining inhibition of autophagy (through ULK1/2) and KRAS (using sotorasib) on KRAS mutant NSCLC making the study valuable to cancer biologists and more broadly in a clinical setting. The evidence generated by GEM mouse models and cell lines is solid but could be further strengthened by increasing the mouse cohort size. This study holds translational relevance beyond NSCLC to other indications that carry KRAS mutations.

Reviewed by eLife

Direct visualization of emergent metastatic features within an ex vivo model of the tumor microenvironment

1. Libi Anandi
2. Jeremy Garcia
3. Manon Ros
4. Libuše Janská
5. Josephine Liu
6. Carlos Carmona-Fontaine

Reviewed by Review Commons

Tumor-infiltrating nerves functionally alter brain circuits and modulate behavior in a mouse model of head-and-neck cancer

1. Jeffrey Barr
2. Austin Walz
3. Anthony C Restaino
4. Moran Amit
5. Sarah M Barclay
6. Elisabeth G Vichaya
7. William C Spanos
8. Robert Dantzer
9. Sebastien Talbot
10. Paola D Vermeer

• Curated by eLife

  eLife assessment

  This important research describes the sensory innervation of oral tumors, with potential implications for understanding cancer-induced alterations in motivation and anhedonia in a mouse model. These findings are solid and are supported by anatomical and transcriptional changes in the tumor that suggest sensory innervation, neural tracing, and neural activity measurements. While nerve innervation of the tumor and associated increase in brain activity is well-supported, future studies could enhance specificity by employing more targeted genetic and pharmacological tools to manipulate these circuits selectively.

Reviewed by eLife

BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas

1. Paul Huchede
2. Swann Meyer
3. Clément Berthelot
4. Maud Hamadou
5. Adrien Bertrand-Chapel
6. Andria Rakotomalala
7. Line Manceau
8. Julia Tomine
9. Nicolas Lespinasse
10. Paul Lewandowski
11. Martine Cordier-Bussat
12. Laura Broutier
13. Aurélie Dutour
14. Isabelle Rochet
15. Jean-Yves Blay
16. Cyril Degletagne
17. Valéry Attignon
18. Angel Montero-Carcaboso
19. Marion Le Grand
20. Eddy Pasquier
21. Alexandre Vasiljevic
22. Pascale Gilardi-Hebenstreit
23. Samuel Meignan
24. Pierre Leblond
25. Vanessa Ribes
26. Erika Cosset
27. Marie Castets

• Curated by eLife

  eLife assessment

  This valuable study examines whether the BMP signaling pathway has a role in H3.3K27M DMG tumors, regardless of the presence of ACRVR1 activating mutations. The authors provide solid evidence that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. Although this work could be further enhanced by the inclusion of additional models, the study overall points to BMP2/7 as a potential target for future therapies in this deadly cancer.

Reviewed by eLife

Insights into metabolic heterogeneity of colorectal cancer gained from fluorescence lifetime imaging

1. Anastasia D Komarova
2. Snezhana D Sinyushkina
3. Ilia D Shchechkin
4. Irina N Druzhkova
5. Sofia A Smirnova
6. Vitaliy M Terekhov
7. Artem M Mozherov
8. Nadezhda I Ignatova
9. Elena E Nikonova
10. Evgeny A Shirshin
11. Liubov E Shimolina
12. Sergey V Gamayunov
13. Vladislav I Shcheslavskiy
14. Marina V Shirmanova

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the heterogeneity of tumour metabolism using fluorescence lifetime imaging, measured across 4 cell lines, 4 tumour types of in vivo mouse models, and 29 patient samples. The indication is that the level of heterogeneity of cellular metabolism increases with model complexity and demonstrates high heterogeneity at a clinical level. The evidence supporting the claims of the authors is solid, and at the revision stage, the authors have included additional samples from 8 patients in the data pool, which is helpful for the conclusions that the authors are trying to draw. The work will be of interest to medical biologists developing methods for quantifying metabolic heterogeneity.

Reviewed by eLife

MDM2 stabilization of Notch intracellular domain upon DNA damage plays a major role in non-small cell lung carcinoma response to platinum chemotherapy

1. Sara Bernardo
2. Quentin-Dominique Thomas
3. Maicol Mancini
4. Alba Santos
5. Sylvia Fenosoa Rasamizafy
6. Amina-Milissa Maacha
7. Anais Giry
8. Emilie Bousquet-Mur
9. Laura Papon
10. Marion Goussard
11. Christophe Fremin
12. Andrea Pasquier
13. María Rodríguez
14. Camille Travert
15. Jean-Louis Pujol
16. Laetitia K Linares
17. Lisa Heron-Milhavet
18. Alexandre Djiane
19. Irene Ferrer
20. Luis Paz-Ares
21. Xavier Quantin
22. Luis M Montuenga
23. Hélène Tourriere
24. Antonio Maraver

Reviewed by Review Commons

Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape

1. Ashley L Cook
2. Surojit Sur
3. Laura Dobbyn
4. Evangeline Watson
5. Joshua D Cohen
6. Blair Ptak
7. Bum Seok Lee
8. Suman Paul
9. Emily Hsiue
10. Maria Popoli
11. Bert Vogelstein
12. Nickolas Papadopoulos
13. Chetan Bettegowda
14. Kathy Gabrielson
15. Shibin Zhou
16. Kenneth W Kinzler
17. Nicolas Wyhs

• Curated by eLife

  eLife assessment

  Here, the authors developed a cell-based screening assay for the identification of small molecule inhibitors of nonsense-mediated decay (NMD), and used it to validate KVS0001, a new small molecule SMG1 kinase inhibitor derived from the existing inhibitor SMG1i-11, showing it inhibits NMD in cultured cells leading to expression of neoantigens from NMD-targeted genes and slows tumor growth of cancer cell lines possessing a significant number of out-of-frame indel mutations. The conclusions are supported by convincing evidence, and the significance of this work consists in the development of a new and very promising NMD inhibitor drug that acts as an inhibitor of the SMG1 NMD kinase and is effective in animal tumor studies. This is an important advance for the field, as previous NMD inhibitors were not specific, lacked efficacy, or were very toxic and hence not suitable for animal applications.

Reviewed by eLife