The evolution of two transmissible cancers in Tasmanian devils DOI
Maximilian R. Stammnitz, Kevin Gori, Young Mi Kwon

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6642), P. 283 - 293

Published: April 20, 2023

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and 2 (DFT2). We investigated the genetic diversity evolution of these clones by analyzing 78 DFT1 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that first emerged in 1986 (1982 1989) 2011 (2009 2012). Subclone analysis documents transmission heterogeneous cell populations. has faster mutation rates than across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, copy number alterations, we identify hypermutated lineage with defective DNA mismatch repair. Several loci show plausible evidence positive selection or DFT2, loss chromosome Y inactivation MGA , but none are common both cancers. This study reveals parallel long-term cancers inhabiting niche devils.

Language: Английский

Mutations and mechanisms of WNT pathway tumour suppressors in cancer DOI
Jeroen M. Bugter, Nicola Fenderico, Madelon M. Maurice

et al.

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 21(1), P. 5 - 21

Published: Oct. 23, 2020

Language: Английский

Citations

348
The next-generation Open Targets Platform: reimagined, redesigned, rebuilt DOI Creative Commons
David Ochoa, Andrew Hercules, Miguel Carmona

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D1353 - D1359

Published: Nov. 18, 2022

The Open Targets Platform (https://platform.opentargets.org/) is an open source resource to systematically assist drug target identification and prioritisation using publicly available data. Since our last update, we have reimagined, redesigned, rebuilt the in order streamline data integration harmonisation, expand ways which users can explore data, improve user experience. gene-disease causal evidence has been enhanced expanded better capture disease causality across rare, common, somatic diseases. For annotations, incorporated new features that help assess safety tractability, including genetic constraint, PROTACtability assessments, AlphaFold structure predictions. We also introduced machine learning applications for knowledge extraction from published literature, clinical trial information, labels. technologies frameworks since update will ease introduction of creation separate instances adapted requirements. Our Community forum, training materials, outreach programme support a range use cases.

Language: Английский

Citations

266
Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment DOI Creative Commons
Xiaoyu Xu, Chang Liu, Yonghui Wang

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 176, P. 113891 - 113891

Published: July 26, 2021

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, extensity used human diseases treatment, especially cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by are established. However, significant challenges remain clinical applications. The greatest challenge therapy how safely efficiently deliver it target sites in vivo. Nanotechnology has greatly contributed drug delivery. Here, we present the action mechanisms CRISPR/Cas9, application focus on nanotechnology-based delivery gene editing immunotherapy pave way translation. We detail difficult barriers CRISIR/Cas9 vivo discuss relative solutions encapsulation, delivery, controlled release, cellular internalization, endosomal escape.

Language: Английский

Citations

181
The road ahead in genetics and genomics DOI
Amy L. McGuire,

Stacey Gabriel,

Sarah A. Tishkoff

et al.

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(10), P. 581 - 596

Published: Aug. 24, 2020

Language: Английский

Citations

173
Genomic and evolutionary classification of lung cancer in never smokers DOI
Tongwu Zhang, Philippe Joubert, Naser Ansari‐Pour

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(9), P. 1348 - 1359

Published: Sept. 1, 2021

Language: Английский

Citations

154
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects DOI Creative Commons

Paul Shafer,

Lauren Kelly,

Valentina Hoyos

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 3, 2022

To redirect T cells against tumor cells, can be engineered

Language: Английский

Citations

152
Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression DOI Creative Commons
Chen Xue,

Ganglei Li,

Juan Lü

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 24, 2021

Circular RNAs (circRNAs), covalently closed noncoding RNAs, are widely expressed in eukaryotes and viruses. They can function by regulating target gene expression, linear RNA transcription protein generation. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays key roles many biological cellular processes, such as cell proliferation, growth, invasion, migration, angiogenesis. It also a pivotal role cancer progression. Emerging data suggest that the circRNA/PI3K/AKT axis modulates expression of cancer-associated genes thus regulates tumor Aberrant regulation circRNAs is significantly associated with clinicopathological characteristics an important functions. In this review, we summarized functions PI3K-AKT-related vitro vivo assessed their associations characteristics. We further discussed diagnosis, prognostication, treatment cancers.

Language: Английский

Citations

146
The SWI/SNF chromatin remodeling complex helps resolve R-loop-mediated transcription–replication conflicts DOI
Aleix Bayona‐Feliú, Sónia Barroso, Sergio Muñoz

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(7), P. 1050 - 1063

Published: May 13, 2021

Language: Английский

Citations

120
Phenotypic plasticity and genetic control in colorectal cancer evolution DOI Creative Commons
Jacob Househam, Timon Heide, George D. Cresswell

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 744 - 753

Published: Oct. 26, 2022

Abstract Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity 1 . The interplay of these biological processes their respective contributions tumour evolution remain unknown. Here we show that genetic ancestry only infrequently affects gene expression traits subclonal in colorectal cancer (CRC). Using spatially resolved paired whole-genome transcriptome sequencing, find the majority variation is not strongly heritable but rather ‘plastic’. Somatic quantitative trait loci analysis identified a number putative controls by cis -acting coding non-coding mutations, which were clonal within tumour, alongside frequent structural alterations. Consistently, computational inference on spatial patterning phylogenies finds considerable proportion CRCs did evidence selection, subset drivers associated subclone expansions. Spatial intermixing clones common, some tumours growing exponentially others at periphery. Together, our data suggest most CRC has no major phenotypic consequence plasticity is, instead, widespread tumour.

Language: Английский

Citations

116
Metallo-Drugs in Cancer Therapy: Past, Present and Future DOI Creative Commons
Roxana Liana Lucaciu, Adriana Corina Hangan, Bogdan Sevastre

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(19), P. 6485 - 6485

Published: Oct. 1, 2022

Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities inherent resistance, systemic toxicity and severe side effects. Out 50% patients administrated to chemotherapy, only 5% survive. For reasons, the identification new drug designs therapeutic strategies that could target cancer cells while leaving normal unaffected still continues be a challenge. Despite advances led development therapies, options are limited for many types cancers. This review provides an overview platinum, copper ruthenium metal based anticancer drugs clinical trials vitro/in vivo studies. Presumably, complexes greater potential than Pt(II) complexes, showing reduced toxicity, mechanism action, different spectrum activity possibility non-cross-resistance. We focus discussion towards past, present future aspects.

Language: Английский

Citations

110