keyword
https://read.qxmd.com/read/38473293/parp-inhibitors-strategic-use-and-optimal-management-in-ovarian-cancer
#1
REVIEW
Nicholas Hirschl, Wildnese Leveque, Julia Granitto, Valia Sammarco, Mervyns Fontillas, Richard T Penson
Poly (ADP-ribose) polymerase (PARP) inhibitors have become an established part of the anticancer armamentarium. Discovered in the 1980s, PARP inhibitors (PARPis) were initially developed to exploit the presence of BRCA mutations, which disrupt the homologous recombination repair of deoxyribonucleic acid (DNA) via synthetic lethality, an intrinsic vulnerability caused by the cell's dependence on other DNA repair mechanisms for which PARP is an essential contributor. PARPi use expanded with the demonstration of clinical benefit when other mechanisms of high-fidelity DNA damage response were present in cancer cells called homologous repair deficiency (HRD)...
February 25, 2024: Cancers
https://read.qxmd.com/read/38464143/detecting-somatic-mutations-without-matched-normal-samples-using-long-reads
#2
Jared T Simpson
DNA sequencing of tumours to identify somatic mutations has become a critical tool to guide the type of treatment given to cancer patients. The gold standard for mutation calling is comparing sequencing data from the tumour to a matched normal sample to avoid mis-classifying inherited SNPs as mutations. This procedure works extremely well, but in certain situations only a tumour sample is available. While approaches have been developed to find mutations without a matched normal, they have limited accuracy or require specific types of input data (e...
February 29, 2024: bioRxiv
https://read.qxmd.com/read/38445359/terra-and-the-alternative-lengthening-of-telomeres-a-dangerous-affair
#3
REVIEW
Claus M Azzalin
Eukaryotic telomeres are transcribed into the long noncoding RNA TERRA. A fraction of TERRA remains associated with telomeres by forming RNA:DNA hybrids dubbed telR-loops. TERRA and telR-loops are essential to promote telomere elongation in human cancer cells that maintain telomeres through a homology-directed repair pathway known as alternative lengthening of telomeres or ALT. However, TERRA and telR-loops compromise telomere integrity and cell viability if their levels are not finely tuned. The study of telomere transcription in ALT cells will enormously expand our understanding of the ALT mechanism and of how genome integrity is maintained...
March 6, 2024: FEBS Letters
https://read.qxmd.com/read/38410476/kras-silencing-impacts-chromatin-organization-and-transcriptional-activity-in-colorectal-cancer-cells
#4
Flávia Martins, Ana Luísa Machado, Andreia Ribeiro, Susana Mendonça Oliveira, Joana Carvalho, Rune Matthiesen, Vadim Backman, Sérgia Velho
Preclinical and clinical data have highlighted the challenges in targeting KRAS mutant tumors, revealing that cancer cells initially sensitive to treatment circumvent KRAS dependence and become tolerant. However, the exact mechanisms governing the transition from a drug-sensitive to a drug-tolerant state remain unclear. Herein, we used 3D culture models of mutant KRAS colorectal cancer cells with distinct KRAS dependencies to show that sensitive and resistant cells undergo distinct chromatin and transcriptional adaptations upon acute KRAS loss...
February 14, 2024: Research Square
https://read.qxmd.com/read/38398168/review-of-related-factors-for-persistent-risk-of-hepatitis-b-virus-associated-hepatocellular-carcinoma
#5
REVIEW
Nevin Varghese, Amry Majeed, Suraj Nyalakonda, Tina Boortalary, Dina Halegoua-DeMarzio, Hie-Won Hann
Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies...
February 14, 2024: Cancers
https://read.qxmd.com/read/38233727/epigenetic-reprogramming-of-t-cells-unlocking-new-avenues-for-cancer-immunotherapy
#6
REVIEW
Vipin Singh, Sandhik Nandi, Aritra Ghosh, Santanu Adhikary, Shravanti Mukherjee, Siddhartha Roy, Chandrima Das
T cells, a key component of cancer immunotherapy, undergo a variety of histone modifications and DNA methylation changes since their bone marrow progenitor stages before developing into CD8+ and CD4+ T cells. These T cell types can be categorized into distinct subtypes based on their functionality and properties, such as cytotoxic T cells (Tc), helper T cells (Th), and regulatory T cells (Treg) as subtypes for CD8+ and CD4+ T cells. Among these, the CD4+ CD25+ Tregs potentially contribute to cancer development and progression by lowering T effector (Teff) cell activity under the influence of the tumor microenvironment (TME)...
January 18, 2024: Cancer Metastasis Reviews
https://read.qxmd.com/read/38213285/composition-preparation-methods-and-applications-of-nanoniosomes-as-codelivery-systems-a-review-of-emerging-therapies-with-emphasis-on-cancer
#7
REVIEW
Maryam Roostaee, Atefeh Derakhshani, Hadiseh Mirhosseini, Elmira Banaee Mofakham, Sonia Fathi-Karkan, Shekoufeh Mirinejad, Saman Sargazi, Mahmood Barani
Nanoniosome-based drug codelivery systems have become popular therapeutic instruments, demonstrating tremendous promise in cancer therapy, infection treatment, and other therapeutic domains. An emerging form of vesicular nanocarriers, niosomes are self-assembling vesicles composed of nonionic surfactants, along with cholesterol or other amphiphilic molecules. This comprehensive review focuses on how nanosystems may aid in making anticancer and antibacterial pharmaceuticals more stable and soluble. As malleable nanodelivery instruments, the composition, types, preparation procedures, and variables affecting the structure and stability of niosomes are extensively investigated...
January 12, 2024: Nanoscale
https://read.qxmd.com/read/38201222/promising-and-minimally-invasive-biomarkers-targeting-melanoma
#8
REVIEW
Pavlina Spiliopoulou, Carlos Diego Holanda Lopes, Anna Spreafico
The therapeutic landscape of malignant melanoma has been radically reformed in recent years, with novel treatments emerging in both the field of cancer immunotherapy and signalling pathway inhibition. Large-scale tumour genomic characterization has accurately classified malignant melanoma into four different genomic subtypes so far. Despite this, only somatic mutations in BRAF oncogene, as assessed in tumour biopsies, has so far become a validated predictive biomarker of treatment with small molecule inhibitors...
December 20, 2023: Cells
https://read.qxmd.com/read/38169606/pharmacological-inhibition-of-myc-to-mitigate-chemoresistance-in-preclinical-models-of-squamous-cell-carcinoma
#9
JOURNAL ARTICLE
Shuo Liu, Zhen Qin, Yaqing Mao, Ning Wang, Wenbo Zhang, Yujia Wang, Yiwen Chen, Lingfei Jia, Xin Peng
Rationale: Cisplatin-based chemotherapy is the first-line treatment for late-stage head and neck squamous cell carcinoma (HNSCC). However, resistance to cisplatin has become a major obstacle for effective therapy. Cancer stem cells (CSCs) are critical for tumor initiation, growth, metastasis, and chemoresistance. How to effectively eliminate CSCs and overcome chemoresistance remains a key challenge. Herein, we confirmed that MYC plays critical roles in chemoresistance, and explored targeting MYC to overcome cisplatin resistance in preclinical models...
2024: Theranostics
https://read.qxmd.com/read/38106049/sc-tusv-ext-single-cell-clonal-lineage-inference-from-single-nucleotide-variants-snv-copy-number-alterations-cna-and-structural-variants-sv
#10
Nishat Anjum Bristy, Xuecong Fu, Russell Schwartz
Clonal lineage inference ("tumor phylogenetics") has become a crucial tool for making sense of somatic evolution processes that underlie cancer development and are increasingly recognized as part of normal tissue growth and aging. The inference of clonal lineage trees from single cell sequence data offers particular promise for revealing processes of somatic evolution in unprecedented detail. However, most such tools are based on fairly restrictive models of the types of mutation events observed in somatic evolution and of the processes by which they develop...
December 8, 2023: bioRxiv
https://read.qxmd.com/read/38100543/transcription-factors-in-the-development-and-treatment-of-immune-disorders
#11
REVIEW
Samantha D Patalano, Paula Fuxman Bass, Juan I Fuxman Bass
Immune function is highly controlled at the transcriptional level by the binding of transcription factors (TFs) to promoter and enhancer elements. Several TF families play major roles in immune gene expression, including NF-κB, STAT, IRF, AP-1, NRs, and NFAT, which trigger anti-pathogen responses, promote cell differentiation, and maintain immune system homeostasis. Aberrant expression, activation, or sequence of isoforms and variants of these TFs can result in autoimmune and inflammatory diseases as well as hematological and solid tumor cancers...
December 15, 2023: Transcription
https://read.qxmd.com/read/38039637/exploring-the-interaction-of-tepotinib-with-calf-thymus-dna-using-molecular-dynamics-simulation-and-multispectroscopic-techniques
#12
JOURNAL ARTICLE
Mohd Amir, Mohd Aamir Qureshi, Ashma Khan, Shahid M Nayeem, Waseem Ayoub Malik, Saleem Javed
In recent times, there has been a surge in the discovery of drugs that directly interact with DNA, influencing gene expression. As a result, understanding how biomolecules interact with DNA has become a major area of research. One such drug is Tepotinib (TPT), an FDA-approved anti-cancer medication known as a MET tyrosine kinase inhibitor, used in chemotherapy for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations. In our study, we adopted both biophysical and in-silico methods to investigate the binding relationship of TPT and ctDNA...
November 23, 2023: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://read.qxmd.com/read/38001670/molecular-biology-and-clinical-management-of-esophageal-adenocarcinoma
#13
REVIEW
Shulin Li, Sanne Johanna Maria Hoefnagel, Kausilia Krishnawatie Krishnadath
Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC...
November 14, 2023: Cancers
https://read.qxmd.com/read/37978130/development-of-homologous-recombination-functional-assays-for-targeting-the-ddr
#14
JOURNAL ARTICLE
Ailsa J Oswald, Charlie Gourley
Identification of tumours that have homologous recombination deficiency (HRD) has become of increasing interest following the licensing of PARP inhibitors. Potential methods to assess HRD status include; clinical selection for platinum sensitive disease, mutational/methylation status, genomic scars/signature and functional RAD51 assays. Homologous recombination (HR) is a dynamic process with the potential to evolve over a disease course, particularly in relation to previous treatment. This is one of the major drawbacks of genomic scars/signatures, as they only demonstrate historic HR status...
2023: Cancer Treatment and Research
https://read.qxmd.com/read/37955972/cell-cycle-responses-to-topoisomerase-ii-inhibition-molecular-mechanisms-and-clinical-implications
#15
JOURNAL ARTICLE
Tanya N Soliman, Daniel Keifenheim, Peter J Parker, Duncan J Clarke
DNA Topoisomerase IIA (Topo IIA) is an enzyme that alters the topological state of DNA and is essential for the separation of replicated sister chromatids and the integrity of cell division. Topo IIA dysfunction activates cell cycle checkpoints, resulting in arrest in either the G2-phase or metaphase of mitosis, ultimately triggering the abscission checkpoint if non-disjunction persists. These events, which directly or indirectly monitor the activity of Topo IIA, have become of major interest as many cancers have deficiencies in Topoisomerase checkpoints, leading to genome instability...
December 4, 2023: Journal of Cell Biology
https://read.qxmd.com/read/37931584/epigenetic-and-inflammatory-markers-in-older-adults-with-cancer-a-young-international-society-of-geriatric-oncology-narrative-review
#16
JOURNAL ARTICLE
Nikesha Gilmore, Kah Poh Loh, Gabor Liposits, Sukeshi Patel Arora, Paula Vertino, Michelle Janelsins
The number of adults aged ≥ 65 years with cancer is rapidly increasing. Older adults with cancer are susceptible to treatment-related acute and chronic adverse events, resulting in loss of independence, reduction in physical function, and decreased quality of life. Nevertheless, evidence-based interventions to prevent or treat acute and chronic adverse events in older adults with cancer are limited. Several promising blood-based biomarkers related to inflammation and epigenetic modifications are available to identify older adults with cancer who are at increased risk of accelerated aging and physical, functional, and cognitive impairments caused by the cancer and its treatment...
November 4, 2023: Journal of Geriatric Oncology
https://read.qxmd.com/read/37922341/csf1r-dependent-macrophages-in-the-salivary-gland-are-essential-for-epithelial-regeneration-after-radiation-induced-injury
#17
JOURNAL ARTICLE
John G McKendrick, Gareth-Rhys Jones, Sonia S Elder, Erin Watson, Wouter T'Jonck, Ella Mercer, Marlene S Magalhaes, Cecilia Rocchi, Lizi M Hegarty, Amanda L Johnson, Christoph Schneider, Burkhard Becher, Clare Pridans, Neil Mabbott, Zhaoyuan Liu, Florent Ginhoux, Marc Bajenoff, Rebecca Gentek, Calum C Bain, Elaine Emmerson
The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis and how they may contribute to tissue repair after injury are not well understood...
November 3, 2023: Science Immunology
https://read.qxmd.com/read/37894302/respiratory-tract-oncobiome-in-lung-carcinogenesis-where-are-we-now
#18
REVIEW
Karolina H Czarnecka-Chrebelska, Jacek Kordiak, Ewa Brzeziańska-Lasota, Dorota Pastuszak-Lewandoska
The importance of microbiota in developing and treating diseases, including lung cancer (LC), is becoming increasingly recognized. Studies have shown differences in microorganism populations in the upper and lower respiratory tracts of patients with lung cancer compared to healthy individuals, indicating a link between dysbiosis and lung cancer. However, it is not only important to identify "which bacteria are present" but also to understand "how" they affect lung carcinogenesis. The interactions between the host and lung microbiota are complex, and our knowledge of this relationship is limited...
October 11, 2023: Cancers
https://read.qxmd.com/read/37884744/nct-dkfz-master-handbook-of-interpreting-whole-genome-transcriptome-and-methylome-data-for-precision-oncology
#19
JOURNAL ARTICLE
Andreas Mock, Maria-Veronica Teleanu, Simon Kreutzfeldt, Christoph E Heilig, Jennifer Hüllein, Lino Möhrmann, Arne Jahn, Dorothea Hanf, Irina A Kerle, Hans Martin Singh, Barbara Hutter, Sebastian Uhrig, Martina Fröhlich, Olaf Neumann, Andreas Hartig, Sascha Brückmann, Steffen Hirsch, Kerstin Grund, Nicola Dikow, Daniel B Lipka, Marcus Renner, Irfan Ahmed Bhatti, Leonidas Apostolidis, Richard F Schlenk, Christian P Schaaf, Albrecht Stenzinger, Evelin Schröck, Daniel Hübschmann, Christoph Heining, Peter Horak, Hanno Glimm, Stefan Fröhling
Analysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities of individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive molecular characterization adds significant clinical value. However, the complexity and heterogeneity of the resulting data are major challenges for disciplines involved in interpretation and recommendations for individualized care, and limited information exists on how to approach multilayered tumor profiles in clinical routine...
October 26, 2023: NPJ Precision Oncology
https://read.qxmd.com/read/37814109/transfer-rnas-as-dynamic-and-critical-regulators-of-cancer-progression
#20
REVIEW
Alexandra M Pinzaru, Sohail F Tavazoie
Transfer RNAs (tRNAs) have been historically viewed as non-dynamic adaptors that decode the genetic code into proteins. Recent work has uncovered dynamic regulatory roles for these fascinating molecules. Advances in tRNA detection methods have revealed that specific tRNAs can become modulated upon DNA copy number and chromatin alterations and can also be perturbed by oncogenic signalling and transcriptional regulators in cancer cells or the tumour microenvironment. Such alterations in the levels of specific tRNAs have been shown to causally impact cancer progression, including metastasis...
November 2023: Nature Reviews. Cancer
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