Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(9), P. 1879 - 1889

Published: April 13, 2023

Immune-checkpoint inhibitors show promising effects in the treatment of multiple tumor types. Biomarkers are biological indicators used to select patients for a systemic anticancer treatment, but there only few clinically useful biomarkers such as PD-L1 expression and mutational burden, which can be predict immunotherapy response. In this study, we established database consisting both gene clinical data identify response anti-PD-1, anti-PD-L1, anti-CTLA-4 immunotherapies. A GEO screening was executed datasets with simultaneously available transcriptomic regardless cancer type. The restricted studies involving administration anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab) or (ipilimumab) agents. Receiver operating characteristic (ROC) analysis Mann-Whitney test were across all genes features related therapy consisted 1434 tissue samples from 19 esophageal, gastric, head neck, lung, urothelial cancers, plus melanoma. strongest druggable candidates linked resistance SPIN1 (AUC = 0.682, P 9.1E-12), SRC 0.667, 5.9E-10), SETD7 0.663, 1.0E-09), FGFR3 0.657, 3.7E-09), YAP1 0.655, 6.0E-09), TEAD3 0.649, 4.1E-08) BCL2 0.634, 9.7E-08). cohort, BLCAP 0.735, 2.1E-06) most candidate. No therapeutically relevant target found predictive cohort. group, able confirm significant correlation survival mismatch-repair MLH1 MSH6. web platform further validation new biomarker set up at https://www.rocplot.com/immune . summary, investigate large cohort solid samples. Our results could help patient cohorts eligible immunotherapy.

Language: Английский

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Artificial intelligence in cancer diagnosis and therapy: Current status and future perspective

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 165, P. 107356 - 107356

Published: Aug. 14, 2023

Language: Английский

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Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2478 - 2478

Published: July 7, 2024

The rise of drug resistance in cancer cells presents a formidable challenge modern oncology, necessitating the exploration innovative therapeutic strategies. This review investigates latest advancements overcoming mechanisms employed by cells, focusing on emerging modalities. intricate molecular insights into resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, promising avenues offered targeted therapies, combination treatments, immunotherapies, precision medicine approaches highlighted. Specifically, synergistic effects combining traditional cytotoxic agents with molecularly inhibitors to circumvent pathways examined. Additionally, evolving landscape immunotherapeutic interventions, immune checkpoint adoptive cell is explored terms bolstering anti-tumor responses evasion mechanisms. Moreover, significance biomarker-driven strategies for predicting monitoring treatment underscored, thereby optimizing outcomes. For future direction paradigms, current focused prevailing challenges improving patient outcomes, through an integrative analysis these

Language: Английский

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Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics

Life Sciences, Journal Year: 2024, Volume and Issue: 345, P. 122613 - 122613

Published: April 4, 2024

Language: Английский

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AI-Assisted Detection of Biomarkers by Sensors and Biosensors for Early Diagnosis and Monitoring

Biosensors, Journal Year: 2024, Volume and Issue: 14(7), P. 356 - 356

Published: July 22, 2024

The steady progress in consumer electronics, together with improvement microflow techniques, nanotechnology, and data processing, has led to implementation of cost-effective, user-friendly portable devices, which play the role not only gadgets but also diagnostic tools. Moreover, numerous smart devices monitor patients' health, some them are applied point-of-care (PoC) tests as a reliable source evaluation patient's condition. Current practices still based on laboratory tests, preceded by collection biological samples, then tested clinical conditions trained personnel specialistic equipment. In practice, collecting passive/active physiological behavioral from patients real time feeding artificial intelligence (AI) models can significantly improve decision process regarding diagnosis treatment procedures via omission conventional sampling while excluding pathologists. A combination novel methods digital traditional biomarker detection portable, autonomous, miniaturized revolutionize medical diagnostics coming years. This article focuses comparison modern techniques AI machine learning (ML). presented technologies will bypass laboratories start being commercialized, should lead or substitution current Their application PoC settings technology accessible every patient appears be possibility. Research this field is expected intensify Technological advancements sensors biosensors anticipated enable continuous real-time analysis various omics fields, fostering early disease intervention strategies. integration health platforms would predictive personalized healthcare, emphasizing importance interdisciplinary collaboration related scientific fields.

Language: Английский

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Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 16, 2024

Abstract TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These efficient regulators of autophagy, apoptosis, innate immune responses confer immunity against viruses bacteria. TRIMs function as receptors or scaffold that target substrates for autophagy-mediated degradation. Most interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting autophagosomes. They regulate functions ATG through physical interactions ubiquitination. affect lipidation MAP1LC3B1 MAP1LC3B2, which is a prerequisite phagophore autophagosome formation. In addition, they MTOR kinase TFEB, regulating expression genes. apoptosis crucial cell proliferation tumor Many intrinsic extrinsic via surface TGFBR2, TNFRSF1A, FAS. Mitochondria modulate anti- proapoptotic BCL2, BAX, BAK1, CYCS. use multipronged approach apoptotic pathways, culminating in coordinated activation inhibition initiator executor CASPs. Furthermore, can have dual effect determining fate therefore cellular homeostasis. this review, we discuss mechanistic insights into role autophagy be used better understand physiology. findings develop therapeutic interventions prevent treat multiple genetic infectious diseases. Graphical

Language: Английский

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Novel biomarkers for early detection of gastric cancer

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(17), P. 2515 - 2533

Published: May 5, 2023

Gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Less than half GC cases are diagnosed at an advanced stage due to its lack early symptoms. is heterogeneous disease associated with number genetic and somatic mutations. Early detection effective monitoring tumor progression essential for reducing burden mortality. The current widespread use semi-invasive endoscopic methods radiologic approaches has increased the treatable cancers: However, these invasive, costly, time-consuming. Thus, novel molecular noninvasive tests that detect alterations seem be more sensitive specific compared methods. Recent technological advances have enabled blood-based biomarkers could used as diagnostic indicators postsurgical minimal residual disease. These include circulating DNA, RNA, extracellular vesicles, proteins, their clinical applications currently being investigated. identification ideal markers high sensitivity specificity would improve survival rates contribute advancement precision medicine. This review provides overview topics regarding novel, recently developed GC.

Language: Английский

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Recent Trends in Biosensing and Diagnostic Methods for Novel Cancer Biomarkers

Biosensors, Journal Year: 2023, Volume and Issue: 13(3), P. 398 - 398

Published: March 18, 2023

Cancer is one of the major public health issues in world. It has become second leading cause death, with approximately 75% cancer deaths transpiring low- or middle-income countries. causes a heavy global economic cost estimated at more than trillion dollars per year. The most common cancers are breast, colon, rectum, prostate, and lung cancers. Many these can be treated effectively cured if detected primary stage. Nowadays, around 50% late stages, to serious complications death. Early diagnosis diseases substantially increases efficient treatment high chances survival. Biosensors potential screening methodologies useful early biomarkers. This review summarizes recent findings about novel biomarkers their advantages over traditional biomarkers, biosensing diagnostic methods for them; thus, this may helpful recognition monitoring response various human

Language: Английский

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Non‐coding RNAs in cancer immunotherapy: Predictive biomarkers and targets

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(9)

Published: Sept. 1, 2023

Abstract Background To date, standardising clinical predictive biomarkers for assessing the response to immunotherapy remains challenging due variations in personal genetic signatures, tumour microenvironment complexities and epigenetic onco‐mechanisms. Main body Early monitoring of key non‐coding RNA (ncRNA) may help predicting efficacy cancer come up with standard ncRNA biomarkers. For instance, reduced miR‐125b‐5p level plasma non‐small cell lung patients treated anti‐PD‐1 predicts a positive outcome. The miR‐153 colorectal chimeric antigen receptor T lymphocyte (CAR‐T) therapy indicate activation T‐cell killing activity. miR‐148a‐3p miR‐375 levels forecast favourable responses CAR‐T‐cell B‐cell acute lymphoblastic leukaemia. In GPC3 peptide vaccine, serum miR‐1228‐5p, miR‐193a‐5p miR‐375‐3p were reported as good improved overall survival. Therefore, there is critical need further studies elaborate on that have potential predict early immunotherapy. Conclusion This review summarises important different immunotherapeutic modalities, including monoclonal antibodies, small molecule inhibitors, vaccines CAR‐T cells. addition, concise discussion forthcoming perspectives provided, outlining technical approaches optimal utilisation immunomodulatory tools therapeutic targets.

Language: Английский

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Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Sept. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Language: Английский

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