Cancer Biology

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

Resistance to PSEN1-selective γ-secretase inhibitors in T-cell acute lymphoblastic leukemia

1. Charlien Vandersmissen
2. Sofie Demeyer
3. Kris Jacobs
4. Lien Boogaerts
5. Sara Gutiérrez Fernández
6. Heidi Segers
7. Lucía Chávez-Gutiérrez
8. Jan Cools

Reviewed by Review Commons

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. Stephen L Lessnick
7. Emily R Theisen

• Curated by eLife

  eLife assessment

  This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide solid-based 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 insight into the underlying oncogenic mechanisms in Ewing sarcoma, despite the inherent limitations of the some of the techniques used.

Reviewed by eLife

Aging represses lung tumorigenesis and alters tumor suppression

1. Emily G. Shuldiner
2. Saswati Karmakar
3. Min K. Tsai
4. Jess D. Hebert
5. Yuning J. Tang
6. Laura Andrejka
7. Minwei Wang
8. Colin R. Detrick
9. Hongchen Cai
10. Rui Tang
11. Dmitri A. Petrov
12. Monte M. Winslow

Reviewed by PREreview

Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases

1. Joakim W Karlsson
2. Vasu R Sah
3. Roger Olofsson Bagge
4. Irina Kuznetsova
5. Munir Iqba
6. Samuel Alsen
7. Sofia Stenqvist
8. Alka Saxena
9. Lars Ny
10. Lisa M Nilsson
11. Jonas A Nilsson

• Curated by eLife

  eLife assessment

  This study presents valuable findings on tumor-reactive T cells in liver metastases of uveal melanoma (UM). The authors conducted single-cell RNA sequencing to identify potential tumor-reactive T cells and used PDX models for functional analysis. The evidence supporting their claims is solid. The work will be of interest to scientists working in the field of uveal melanoma.

Reviewed by eLife

Androgen deprivation triggers a cytokine signaling switch to induce immune suppression and prostate cancer recurrence

1. Kai Sha
2. Renyuan Zhang
3. Aerken Maolake
4. Shalini Singh
5. Gurkamal Chatta
6. Kevin H Eng
7. Kent L Nastiuk
8. John J Krolewski

• Curated by eLife

  eLife assessment

  This study presents a potentially valuable finding regarding the role of cytokine signaling in the mechanism of response and resistance to castration therapy in prostate cancer. The evidence, although solid for some aspects of the work, is incomplete and only partially supports the main claims.

Reviewed by eLife

NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model

1. Ismail M Meraz
2. Mourad Majidi
3. Renduo Song
4. Feng Meng
5. Lihui Gao
6. Qi Wang
7. Jing Wang
8. Elizabeth J Shpall
9. Jack A Roth

• Curated by eLife

  eLife assessment

  This study provides a novel and promising NPRL2 gene therapy for enhanced immunotherapy response in a KRAS/STK11 mutant anti-PD1 resistant metastatic NSCLC humanized mouse model. Overall, the authors presented a large amount of convincing in vivo data to demonstrate that NPRL2 gene therapy induces antitumor activity through DC-mediated antigen presentation and cytotoxic immune cell activation. This work will be of interest and useful to medical biologists and oncologists in the research field of KRAS-mutant NSCLC.

Reviewed by eLife

PITAR, a DNA damage-inducible cancer/testis long noncoding RNA, inactivates p53 by binding and stabilizing TRIM28 mRNA

1. Samarjit Jana
2. Mainak Mondal
3. Sagar Mahale
4. Bhavana Gupta
5. Kaval Reddy Prasasvi
6. Lekha Kandasami
7. Neha Jha
8. Abhishek Chowdhury
9. Vani Santosh
10. Chandrasekhar Kanduri
11. Kumaravel Somasundaram

• Curated by eLife

  eLife assessment

  This important study reports, with convincing evidence, that a long non-coding RNA disrupts the activity of the tumor suppressor p53 to contribute to the growth and therapeutic response of glioblastoma. The work will be relevant to scientists working on non-coding RNAs and brain tumors.

Reviewed by eLife