Cancer Biology

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

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

Dual targeting of histone deacetylases and MYC as potential treatment strategy for H3-K27M pediatric gliomas

1. Danielle Algranati
2. Roni Oren
3. Bareket Dassa
4. Liat Fellus-Alyagor
5. Alexander Plotnikov
6. Haim Barr
7. Alon Harmelin
8. Nir London
9. Guy Ron
10. Noa Furth
11. Efrat Shema

• Curated by eLife

  eLife assessment

  This work contributes to the study of H3-K27M mutated pediatric gliomas. It convincingly demonstrates that the concomitant targeting of histone deacetylases (HDACs) and the transcription factor MYC results in a notable reduction in cell viability and tumor growth. This reduction is linked to the suppression of critical oncogenic pathways, particularly mTOR signaling, emphasizing the role of these pathways in the disease's pathogenesis. The current version of the manuscript is important because it unveils a vulnerability from dual targeting HDACs and MYC in the context of pediatric gliomas. This work will be of interest to cancer epigenetics and therapeutics research, with a focus on the neuro-oncology field.

Reviewed by eLife

Timing of treatment shapes the path to androgen receptor signaling inhibitor resistance in prostate cancer

1. Eugine Lee
2. Zeda Zhang
3. Chi-Chao Chen
4. Danielle Choi
5. Aura C. Agudelo Rivera
6. Eliot Linton
7. Yu-jui Ho
8. Jillian Love
9. Justin LaClair
10. John Wongvipat
11. Charles L. Sawyers

• Curated by eLife

  eLife assessment

  This important study provides new insight into the dynamics that underlie the development of therapy resistance in prostate cancer by revealing that divergent tumor evolutionary paths occur in response to different treatment timing and that these converge on common resistance mechanisms. The use of barcoded lineage tracing and characterization of isolated tumor clonal populations provides compelling evidence supporting the importance of clonal dynamics in a tumor ecosystem for treatment resistance. Several open questions remain, however, raising the possibility of alternative interpretations of the data set in its current form. Overall, the findings deepen our understanding of prostate cancer evolution and hold promising implications for how drug resistance can be addressed or prevented.

Reviewed by eLife

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells

1. Pirunthan Perampalam
2. James I MacDonald
3. Komila Zakirova
4. Daniel T Passos
5. Sumaiyah Wasif
6. Yudith Ramos-Valdes
7. Maeva Hervieu
8. Patrick Mehlen
9. Rob Rottapel
10. Benjamin Gibert
11. Rohann JM Correa
12. Trevor G Shepherd
13. Frederick A Dick

• Curated by eLife

  eLife assessment

  The authors further corroborated their model that Netrin signaling promotes survival and dissemination of non-proliferating ovarian cancer cells. These valuable results were found to be of significant potential interest to cancer biologists in as much as they address gaps in knowledge pertinent to the mechanisms underpinning ovarian cancer spread. In general, it was thought that solid experimental evidence was provided to support the role of Netrin signaling in fueling ovarian cancer progression.

Reviewed by eLife

Elevated FOXG1 supports exit from quiescence in neural stem cells through FoxO6

1. Kirsty M Ferguson
2. Carla Blin
3. Claudia Garcia-Diaz
4. Harry Bulstrode
5. Raul Bardini Bressan
6. Katrina McCarten
7. Steven M. Pollard

Reviewed by Review Commons

Tissue-resident natural killer cells support survival in pancreatic cancer through promotion of cDC1-CD8 T activity

1. Simei Go
2. Constantinos Demetriou
3. Giampiero Valenzano
4. Sophie Hughes
5. Simone Lanfredini
6. Helen Ferry
7. Edward Arbe-Barnes
8. Shivan Sivakumar
9. Rachel Bashford-Rogers
10. Mark R Middleton
11. Somnath Mukherjee
12. Jennifer Morton
13. Keaton Jones
14. Eric O Neill

• Curated by eLife

  eLife assessment

  This valuable manuscript provides an interesting account documenting the role of resident CD56(br) NK cells in driving interaction with dendritic cells that attract CD8+ T cells to the pancreas cancer tumor microenvironment (TME). The work convincingly illustrates how irradiation combined with CCR5i and PD1 blockade leads to a reduction in pancreatic cancer growth that correlates with a reduction in Treg cells and enhancement of NK and CD8 T cells in the TME. The correlation of NKC1 signature with survival in pancreatic cancer patients is indeed of broader interest regarding potential relevance to other types of cancer.

Reviewed by eLife

A syngeneic spontaneous zebrafish model of tp53-deficient, EGFRvIII, and PI3KCAH1047R-driven glioblastoma reveals inhibitory roles for inflammation during tumor initiation and relapse in vivo

1. Alex Weiss
2. Cassandra D'Amata
3. Bret J Pearson
4. Madeline N Hayes

• Curated by eLife

  eLife assessment

  This study presents a valuable syngeneic zebrafish model for studying glioblastoma and will be of interest to neuro-oncologists and cancer biologists. Using a feasible in vivo model to study the tumour microenvironment, cell/cell interaction, and immunity, the data are compelling, and opens up new lines of inquiries for future investigation on the impact of efferocytosis on tumor progression and cell of origin in this model as well as assessments of drug resistance mechanisms, using inhibitors to MAPK , Akt and/or mTOR pathway.

Reviewed by eLife