Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 718 - 733
Published: Sept. 10, 2024
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2269 - 2287.e16
Published: April 1, 2024
Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies an autosomal tumor suppressor gene. Here, we report the glycolytic metabolite methylglyoxal (MGO) transiently bypasses by inactivating breast cancer protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic mutations predispose these changes. An analogous SBS signature, again without biallelic inactivation, accompanies MGO accumulation and DNA damage Kras-driven, Brca2-mutant murine pancreatic cancers human cancers. triggers proteolysis, temporarily disabling BRCA2's suppressive functions repair replication, causing functional haploinsufficiency. Intermittent exposure incites episodic permanent inactivation. Thus, metabolic mechanism wherein MGO-induced haploinsufficiency two-hit requirement could link glycolysis activation oncogenes, disorders, dietary challenges signatures implicated evolution.
Language: Английский
Citations
20
Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 2, 2025
Language: Английский
Citations
12
Cell Research, Journal Year: 2025, Volume and Issue: 35(1), P. 11 - 22
Published: Jan. 3, 2025
Abstract Genomic instability is a hallmark of cancer and major driving force tumorigenesis. A key manifestation genomic the formation extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct chromosomes. Ontological studies have revealed that ecDNA serves as carrier oncogenes, immunoregulatory genes, enhancers, capable elevated transcription its cargo genes heterogeneity, leading rapid tumor evolution therapy resistance. Although was documented over half century ago, past decade has witnessed surge breakthrough discoveries about biological functions. Here, we systematically review modern biology uncovered last ten years, focusing on how during this pioneering stage illuminated our understanding ecDNA-driven transcription, progression. Furthermore, discuss ongoing efforts target novel approach therapy. This burgeoning field entering new phase, poised reshape knowledge therapeutic strategies.
Language: Английский
Citations
5
PLoS Biology, Journal Year: 2025, Volume and Issue: 23(3), P. e3003052 - e3003052
Published: March 18, 2025
Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea is a ‘genetic disease’, as posited by somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis caused cancer-driving mutations clonal expansion. However, results from tumor sequencing, motivated genetic paradigm itself, create apparent ‘paradoxes’ are not conducive pure SMT. But beyond causation, new lend credence old ideas organismal biology. To resolve inconsistencies between biological reality, we must complement deep with thinking: embrace formal historicity entities, (re)consider non-genetic plasticity cells tissues. Essay, discuss concepts cell state dynamics tissue fields emerge collective action genes in their morphogenetic context, respectively, how they help explain data context
Language: Английский
Citations
3
Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(12), P. 915 - 931
Published: Oct. 4, 2022
Language: Английский
Citations
70
Cancers, Journal Year: 2022, Volume and Issue: 14(6), P. 1384 - 1384
Published: March 8, 2022
Human solid malignancies harbour a heterogeneous set of cells with distinct genotypes and phenotypes. This heterogeneity is installed at multiple levels. A biological diversity commonly observed between tumours from different patients (inter-tumour heterogeneity) cannot be fully captured by the current consensus molecular classifications for specific cancers. To extend complexity in cancer, there are substantial differences cell to within an individual tumour (intra-tumour heterogeneity, ITH) features cancer evolve space time. Currently, treatment-decision making usually relies on characteristics limited tissue sample time diagnosis or disease progression but does not take into account bulk their constant evolution over In this review, we explore extent emphasis ITH report mechanisms that promote sustain We summarise clinical strikes management cancer. Finally, discuss material technological approaches relevant adequately appreciate ITH.
Language: Английский
Citations
65
Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(8), P. 1192 - 1201
Published: Aug. 1, 2022
Language: Английский
Citations
60
Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)
Published: May 10, 2022
Abstract Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy widely accepted as non-invasive method diagnosing cancer other diseases. We have reviewed the evidence that shows how molecular alterations involved BrM, majorly from breast (BC), lung (LC), melanoma, an inception they can be employed biomarker development. discussed genetic epigenetic changes influence cells to breach blood-brain barrier (BBB) help establish metastatic lesions uniquely distinct brain microenvironment. Keeping abreast recent breakthroughs context of various biomolecules detections identifications, circulating tumor (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, metabolites pursued human body fluids such blood, serum, cerebrospinal fluid (CSF), urine obtain potential candidates The liquid biopsy-based overlay current imaging techniques amplify signal viable improving detection treatments occult BrM.
Language: Английский
Citations
48
Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 931 - 931
Published: March 13, 2023
Cancer is a multifaceted disease that results from the complex interaction between genetic and environmental factors. mortal with biggest clinical, societal, economic burden. Research on better methods of detection, diagnosis, treatment cancer crucial. Recent advancements in material science have led to development metal–organic frameworks, also known as MOFs. MOFs recently been established promising adaptable delivery platforms target vehicles for therapy. These constructed fashion offers them capability drug release stimuli-responsive. This feature has potential be exploited therapy externally led. review presents an in-depth summary research conducted date field MOF-based nanoplatforms therapeutics.
Language: Английский
Citations
44
Oncogene, Journal Year: 2023, Volume and Issue: 42(9), P. 665 - 678
Published: Jan. 3, 2023
Abstract To understand how malignant tumors develop, we tracked cell membrane, nuclear spindle, and cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single underwent traditional mitosis to generate tissue with uniform size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, fusion, karyokinesis without cytokinesis. restitution fragmentation, micronuclei increase contents heterogeneity. At cellular level, development was associated forming transient intracellular cells, termed fecundity cells. The can be decellularized facilitate fusion synchronized other nuclei for subsequent replication. undergo several rounds entosis form complex structures, structures. multiple modes replication absence cytokinesis leads an nuclear-to-cytoplasmic (N/C) ratio reproduction, which is remarkably similar mode division pre-embryogenesis. Our data support that may represent a central regulator histogenesis, intratumoral heterogeneity, immune escape, macroevolution de-repression suppressed pre-embryogenic program somatic
Language: Английский
Citations
38