Cancer Biology

YAP / BRD4 ‐controlled ROR1 promotes tumor‐initiating cells and hyperproliferation in pancreatic cancer

1. Masaya Yamazaki
2. Shinjiro Hino
3. Shingo Usuki
4. Yoshihiro Miyazaki
5. Tatsuya Oda
6. Mitsuyoshi Nakao
7. Takaaki Ito
8. Kazuya Yamagata

Reviewed by Review Commons

Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling

1. Mengyang Fan
2. Wenchao Lu
3. Jianwei Che
4. Nicholas P Kwiatkowski
5. Yang Gao
6. Hyuk-Soo Seo
7. Scott B Ficarro
8. Prafulla C Gokhale
9. Yao Liu
10. Ezekiel A Geffken
11. Jimit Lakhani
12. Kijun Song
13. Miljan Kuljanin
14. Wenzhi Ji
15. Jie Jiang
16. Zhixiang He
17. Jason Tse
18. Andrew S Boghossian
19. Matthew G Rees
20. Melissa M Ronan
21. Jennifer A Roth
22. Joseph D Mancias
23. Jarrod A Marto
24. Sirano Dhe-Paganon
25. Tinghu Zhang
26. Nathanael S Gray

• Curated by eLife

  Evaluation Summary:

  Fan and colleagues disclose the development of covalent TEAD inhibitors and they report on the therapeutic potential of this class of agents in the treatment of TEAD-YAP-driven cancers (e.g., malignant pleural mesothelioma, MPM). Optimized derivatives of a previously reported covalent TEAD inhibitor are described and characterized, using diverse profiling approaches that range from biochemical and cell-based assays to X-ray co-crystallographic analysis and in vivo efficacy in a relevant mouse xenograft model. The manuscript represents an impressive and deep characterization of this small molecule class. The authors' claims and conclusions are very well supported and justified by the data, although differentiation from a very closely related compound termed K-975 is not entirely clear as currently presented.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair

1. Judit Jimenez-Sainz
2. Joshua Mathew
3. Gemma Moore
4. Sudipta Lahiri
5. Jennifer Garbarino
6. Joseph P Eder
7. Eli Rothenberg
8. Ryan B Jensen

• Curated by eLife

  Evaluation Summary:

  This study provides a thorough functional analysis of three mutations in the BRCA2 gene that do not seem to necessarily cause breast cancer. The authors use functional assays in cancer cells and with recombinant proteins to determine that two BRCA2 variants, S1221P and T1980I, are indeed pathogenic, while the T13461 variant is fully functional and benign. The strength of the study is the rigorous assessment of these mutations in a variety of established assays for BRCA2. The work is likely to have a broad impact in the breast cancer field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)

1. Ling Zhong
2. Peng Hao
3. Qian Zhang
4. Tao Jiang
5. Huan Li
6. Jialing Xiao
7. Chenglong Li
8. Lan Luo
9. Chunbao Xie
10. Jiang Hu
11. Liang Wang
12. Yuping Liu
13. Yi Shi
14. Wei Zhang
15. Bo Gong

• Curated by eLife

  Evaluation Summary:

  This paper is of potential interest to a broad audience across myeloma study and single cell technology, as it implies a major adjustment to our current understanding of pathogenesis and treatment of myeloma. Overall the data quality is good, although reasonable alternative explanations of the data can be identified.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability

1. YiQing Lü
2. Tiffany Cho
3. Saptaparna Mukherjee
4. Carmen Florencia Suarez
5. Nicolas S Gonzalez-Foutel
6. Ahmad Malik
7. Sebastien Martinez
8. Dzana Dervovic
9. Robin Hyunseo Oh
10. Ellen Langille
11. Khalid N Al-Zahrani
12. Lisa Hoeg
13. Zhen Yuan Lin
14. Ricky Tsai
15. Geraldine Mbamalu
16. Varda Rotter
17. Patricia Ashton-Prolla
18. Jason Moffat
19. Lucia Beatriz Chemes
20. Anne-Claude Gingras
21. Moshe Oren
22. Daniel Durocher
23. Daniel Schramek

Reviewed by Review Commons

Arginase 1 is a key driver of immune suppression in pancreatic cancer

1. Rosa E Menjivar
2. Zeribe C Nwosu
3. Wenting Du
4. Katelyn L Donahue
5. Hanna S Hong
6. Carlos Espinoza
7. Kristee Brown
8. Ashley Velez-Delgado
9. Wei Yan
10. Fatima Lima
11. Allison Bischoff
12. Padma Kadiyala
13. Daniel Salas-Escabillas
14. Howard C Crawford
15. Filip Bednar
16. Eileen Carpenter
17. Yaqing Zhang
18. Christopher J Halbrook
19. Costas A Lyssiotis
20. Marina Pasca di Magliano

• Curated by eLife

  Evaluation Summary:

  Menjivar et al. identify a previously unrecognized role of myeloid cell Arginase1 (Arg1) activity in shaping the anti-tumor immune response in pancreatic ductal adenocarcinoma (PDAC). The proposed therapeutic combination is a new approach for pancreatic cancer, with an enhanced response to immune therapy upon arginase inhibition.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Machine learning-assisted elucidation of CD81–CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

1. Erika K Ramos
2. Chia-Feng Tsai
3. Yuzhi Jia
4. Yue Cao
5. Megan Manu
6. Rokana Taftaf
7. Andrew D Hoffmann
8. Lamiaa El-Shennawy
9. Marina A Gritsenko
10. Valery Adorno-Cruz
11. Emma J Schuster
12. David Scholten
13. Dhwani Patel
14. Xia Liu
15. Priyam Patel
16. Brian Wray
17. Youbin Zhang
18. Shanshan Zhang
19. Ronald J Moore
20. Jeremy V Mathews
21. Matthew J Schipma
22. Tao Liu
23. Valerie L Tokars
24. Massimo Cristofanilli
25. Tujin Shi
26. Yang Shen
27. Nurmaa K Dashzeveg
28. Huiping Liu

Reviewed by Review Commons

Adrenal cortex size, homeostasis and tumorigenesis is regulated by gonadal hormones via androgen receptor/β-catenin signalling crosstalk

1. Rodanthi Lyraki
2. Anaëlle Grabek
3. Amélie Tison
4. Mirko Peitzsch
5. Nicole Bechman
6. Sameh A Youssef
7. Alain de Bruin
8. Elvira R.M. Bakker
9. Frank Claessens
10. Marie-Christine Chaboissier
11. Andreas Schedl

Reviewed by Review Commons

Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis

1. Juan J Apiz Saab
2. Lindsey N Dzierozynski
3. Patrick B Jonker
4. Roya AminiTabrizi
5. Hardik Shah
6. Rosa Elena Menjivar
7. Andrew J Scott
8. Zeribe C Nwosu
9. Zhou Zhu
10. Riona N Chen
11. Moses Oh
12. Colin Sheehan
13. Daniel R Wahl
14. Marina Pasca di Magliano
15. Costas A Lyssiotis
16. Kay F Macleod
17. Christopher R Weber
18. Alexander Muir

• Curated by eLife

  Evaluation Summary:

  This study builds on previous observations of arginine depletion in the pancreatic tumor microenvironment, with the goal of developing and using a cell culture medium (TIFM) that better recapitulates nutrient levels in the TME. With this system, the authors identify arginine biosynthesis as an adaptation of pancreatic cancer cells to arginine starvation. This work reinforces a timely message that builds upon the push for optimizing and reformulating cell culture media, so as to improve fidelity, and better recapitulation of physiological/pathophysiological cellular behavior. The latter is in turn critical for translational and therapeutic applications. The work will be of interest to tumor biologists.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression

1. Nehal Gupta
2. Hanbing Song
3. Wei Wu
4. Rovingaile K Ponce
5. Yone K Lin
6. Ji Won Kim
7. Eric J Small
8. Felix Y Feng
9. Franklin W Huang
10. Ross A Okimoto

• Curated by eLife

  Evaluation Summary:

  This paper provides insight into a potentially new genetically defined subset of prostate tumors driven by concurrent loss of two tumor suppressor genes. This study both validates previous findings and provides new data that is compelling overall. With some additional statistical and biochemical evidence to support the conclusions, the work would be of interest to cancer biologists studying molecular mechanisms of prostate cancer.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife