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In honour of World Cancer Day, a global initiative that seeks to unite the effort to fight cancer, the editors at Communications Biology have selected some of our most exciting articles in cancer research from the last year to reflect on this ongoing journey. We contemplate the many emerging techniques that are furthering our understanding to improve the diagnosis, treatment and prevention processes, and look forward to another year of exciting developments.
Grimaldi and Cammarata et al. develop a proteomics-based, target discovery platform to identify immunogenic proteins specific to apoptotic tumor cells. This study highlights the importance of protein modifications in apoptotic tumor cells as a mechanism of generating immunogenic neoantigens that can be targeted for T cell-based immunotherapy.
Waaler et al. show that a tankyrase inhibitor, G007-LK, decreases WNT/β-catenin and YAP signaling, sensitizing tumors to anti-PD-1 immune checkpoint therapy in mice. This study suggests that a combinatorial therapy using tankyrase inhibition can be used to overcome β-catenin-mediated resistance to immune checkpoint blockade in melanoma.
Pflügler, Svinka et al. identify a subset of Paneth cells in mouse intestinal crypts and tumors, which express the immune checkpoint molecule Ido1 in a Stat1-dependent manner and promote tumor growth. Gene expression data from human colorectal cancer (CRC) suggest that a similar population is present in human cancer and opens the door for further studies of immune escape mechanisms in CRC.
Dimple Chakravarty et al. review the rapidly emerging data indicating a higher rate of SARS-CoV-2 infection in men. They note that men in the age group most at risk of infection are also at high risk of prostate cancer, and explore the potential links between these diseases and implications for COVID-19 treatment in prostate cancer patients.
Jeremy To et al. develop an ultra-high-content assay platform used to interrogate T-cell-mediated killing of 3D multicellular tumor spheroids. They screen 1,800 annotated compounds to identify small molecules that enhance cytotoxic CD8+ T-cell activity in an antigen-dependent manner, demonstrating the utility of this assay platform.
Geis et al. investigate the potential application of hemibodies, a pair of complementary antibody fragments that redirect T cells against cancer-defining antigen combinations, such as CD38 and SLAMF7, to target multiple myeloma. Their study provides evidence that hemibodies can be developed for effective immunotherapy against multiple myeloma.
Shuai Jiang discusses the regulation and functional role of the Tet2 enzyme, a regulator of lymphoid and myeloid cell development frequently mutated in haematopoietic cancers. He highlights how Tet2 activity may be modulated to influence cancer immune responses.
Hoffman et al characterise the transcriptional response to glucocorticoids in single breast cancer cells in culture. They discover a heterogeneous response and identify over 100 target genes not detected by bulk RNA sequencing, illustrating the power of single cell sequencing and informing on the hormone response in breast cancer.
Erik Knudsen et al. present a pan-cancer analysis of the RB tumor suppressor protein pathway in 31 tumor types. They find that pathway deregulation is multi-faceted with context dependent association with survival. However, gene expression features are surprisingly invariant and support new therapeutic targets.
Pladsen et al. develop Copy Aberration Regional Mapping Analysis (CARMA), an algorithm that derives motifs for copy number profiles in breast cancers by integrating several features, to predict breast cancer prognosis and stratifications. Their algorithm can detect replication and repair defects and can be used in personalized medicine.
Kuang-Yui Chen et al. show that histone H3.3 K27M and G34R mutations share key oncogenic mechanisms such as activation of neurogenesis and NOTCH pathway genes. They find that H3.3 mutant gliomas are sensitive to inhibition of the NOTCH pathway, suggesting a potentially targetable pathway in pediatric gliomas.
Niemöller et al. describe a bisulfite-free assay to assess epigenomics and genomics of single cells (epi-gSCAR). epi-gSCAR generates accurate and reproducible measurements of global DNA methylation and genetic variants at the single cell level, allowing for in-depth analyses of cell-to-cell heterogeneity.
Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.
Paula Granado-Martínez, Sara Ortega, Elena González-Sánchez et al. report a functional analysis of four cancer-associated mutant isoforms of the gene STK11 using cell-based and animal models. They find the mutant isoforms no longer show tumor suppressor activity, promote tumor growth, and affect the regulation of cytokines and genes involved in vesicle trafficking.
Sinha et al. demonstrate that overexpression of centrosomal protein Cep55 in mice is sufficient to cause a wide-spectrum of cancer via multiple mechanisms including hyperactivation of the Pi3k/Akt pathway, stabilized microtubules and a defective replication checkpoint response. These findings are relevant to human cancers as high CEP55 expression is associated with worse prognosis across multiple cancer types.
Yuki Shibayama et al. find that high expression of (pro)renin receptor [(P)RR] in human pancreatic ductal cells causes increased genomic instability, leading to the development of pancreatic ductal adenocarcinoma. They show that (P)RR exerts its carcinogenic effects through direct binding and activation of the chromatin regulator SMARCA5.
Xiaoding Hu et al. find that expression of the proteoglycan decorin is decreased in patients with inflammatory breast cancer compared to normal breast tissue and some other types of breast cancer. They demonstrate that decorin acts as a tumor suppressor in cancer cells and human xenograft mouse models by destabilizing the E-cadherin-EGFR signaling axis, and their findings suggest potential therapeutic strategies for this aggressive breast cancer.
Wu et al. identify an inhibitor to the RNA-binding protein HuR, KH-3, that disrupts the interaction between HuR and target RNAs and inhibits human cancer growth and metastasis in mouse xenograft assays. This study suggests the therapeutic potential of targeting HuR in breast cancer with HuR overexpression.
Toshiro Moroishi is an Associate Professor at the Department of Molecular Enzymology at Kumamoto University, Japan where he has led his own group since December 2017. Research in his lab is focused on the role and regulation of Hippo signalling in development and cancer with a specific interest in the role for Hippo in immunosuppression. He tells us about his research interests, career and lessons learned along the way, as part of our series on early-career researchers.
Dr. Lovorka Stojic is a postdoctoral research fellow at the University of Cambridge and will start her own research group at the Barts Cancer Institute this fall. Her research focuses on understanding how long noncoding RNAs and RNA-binding proteins regulate key cellular processes and how dysregulation of these processes can contribute to human diseases such as cancer. As part of our series on early-career researchers, we asked Dr. Stojic to tell us about her research and career path. She also shares her challenges from juggling between multiple roles and advice for job applications.
Dr. Benjamin Bitler began his independent career at University of Colorado in January 2017. In this short Q&A he tells us about his motivation and passion for research, advice he would give to his younger self, and the attributes of cancer cells that he finds most perplexing.
Dr. Alexander Wyatt is a Senior Research Scientist at the Vancouver Prostate Centre and Assistant Professor at the University of British Columbia. His research uses genomics and bioinformatics to understand lethal prostate and bladder cancer and identify potential new targets for therapy. In this latest instalment of our series highlighting early-career researchers in biology, Dr. Wyatt tells us about research interests and career and about the challenges of the demanding research faculty workload. We’re sure many of our readers will appreciate Dr. Wyatt’s advice on the importance of learning to say “no”.