Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 7(4), С. 967 - 990

Опубликована: Март 19, 2024

Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized effective disease management. Identification key driver mutations molecular profiling have deepened our comprehension genetic alterations in cancer, facilitating targeted therapy immunotherapy selection. Biomarkers such as microsatellite instability (MSI) DNA mismatch repair deficiency (dMMR) guide decisions, opening avenues for immunotherapy. Emerging liquid biopsies, artificial intelligence, machine learning promise to revolutionize early detection, monitoring, selection precision medicine. Despite these advancements, ethical regulatory challenges, including equitable access data privacy, emphasize importance responsible implementation. The dynamic nature with its tumor heterogeneity clonal evolution, underscores necessity adaptive strategies. future lies potential enhance patient care, clinical outcomes, understanding this intricate disease, marked by ongoing evolution field. current reviews focus on providing in-depth knowledge various diverse approaches utilized against at both biochemical levels.

Язык: Английский

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Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands

Therapeutic Advances in Vaccines and Immunotherapy, Год журнала: 2023, Номер 11

Опубликована: Янв. 1, 2023

Checkpoint markers and immune checkpoint inhibitors have been increasingly identified developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel checkpoints their ligands, the precise roles of therapeutic functions, well broad identification counterpart receptors, remain be addressed. In this context, it has suggested that putative receptors can induced upon activation. tumor microenvironment, T cells, crucial response against malignant diseases other central effector such natural killer are regulated via co-stimulatory or co-inhibitory signals from cells. Studies shown exposure cells antigens upregulates expression inhibitory leading T-cell dysfunction exhaustion. Although targeting regulators relative clinical efficacy some types, most trials field cancer immunotherapies revealed unsatisfactory results due de novo adaptive resistance patients. To overcome these obstacles, combinational therapies with newly discovered molecules combined blockage several provide a rationale for further research. Moreover, counterparts at is likely promise effective therapies. review, we examine prospects application emerging checkpoints, immunoglobulin mucin domain 3, lymphocyte activation gene-3, immunoreceptor Ig ITIM domains (TIGIT), V-domain suppressor (VISTA), new B7 family proteins, B- attenuator, association immunotherapy malignancies. addition, biological significance discussed, including cancers, along T-cell-mediated responses.

Язык: Английский

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The Importance of HHLA2 in Solid Tumors—A Review of the Literature

Cells, Год журнала: 2024, Номер 13(10), С. 794 - 794

Опубликована: Май 7, 2024

Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host's immune mechanisms inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, its ligand PD-L1 are used in various therapies. However, most thoroughly researched pathway PD-1/PD-L1 has many limitations, multiple malignancies resist effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) youngest molecule from B7 family. HHLA2/TMIGD2/KIRD3DL3 one critical pathways modulating response. Recent studies have demonstrated HHLA2 double effect system. The connection with TMIGD2 induces T cell growth cytokine production via an AKT-dependent signaling cascade. On other hand, binding KIR3DL3 leads inhibition cells mediates tumor resistance against NK This review aimed summarize novel information about HHLA2, focusing on immunological clinical features HHLA2/KIR3DL3/TMIGD2 context potential strategies for malignancy treatment.

Язык: Английский

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B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours

Cancers, Год журнала: 2023, Номер 15(12), С. 3136 - 3136

Опубликована: Июнь 10, 2023

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale grading. Moreover, we analyzed B7H3-related pathways using available online datasets immunological context expression, through 48-cytokine screening panel cancer tissues homogenates, immunogenic features immune composition. included 158 patients diagnosed with CRC. To levels, performed an immunohistochemistry method (IHC) enzyme-linked immunosorbent assay (ELISA). elucidate composition colorectal cancer, Bio-Plex Pro Human panel. biological characteristics B7H3, used databases. Expression was upregulated in CRC tumour comparison adjacent noncancerous margin tissues. concentrations tumours were positively associated T parameter negatively score. Additionally, Principal Component Analysis showed that correlated cytokines M2-macrophages protumour growth factors. independent status. These findings will improve our understanding role immunity. Our suggests B7-H3 is a promising potential target for therapy. Further studies must clarify mechanisms overexpression its therapeutic importance cancer.

Язык: Английский

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B7-H7: A potential target for cancer immunotherapy

International Immunopharmacology, Год журнала: 2023, Номер 121, С. 110403 - 110403

Опубликована: Июнь 7, 2023

Cancer immunotherapy enhances the body's immunity against tumors by mitigating immune escape. Compared with traditional chemotherapy, has advantages of fewer drugs, a wider range action and side effects. B7-H7 (also known as HHLA2, B7y) is member B7 family costimulatory molecules that was discovered more than 20 years ago. mostly expressed in organs such breast, intestine, gallbladder placenta detected predominantly monocytes/macrophages system. Its expression upregulated after stimulation inflammatory factors lipopolysaccharide interferon-γ. B7-H7/transmembrane immunoglobulin domain containing 2 (TMIGD2) killer cell immunoglobulin-like receptor, three Ig domains long cytoplasmic tail 3 (KIR3DL3)-B7-H7 are two currently confirmed signaling pathways for B7-H7. An increasing number studies have demonstrated widely present variety human tumor tissues, especially programmed death-1 (PD-L1)-negative tumors. promotes progression, disrupts T-cell-mediated antitumor immunity, inhibits surveillance. also triggers escape associated clinical stage, depth infiltration, metastasis, prognosis, survival related to different types. Multiple shown promising immunotherapeutic target. Herein, review current literature on expression, regulation, receptors function its regulation/function

Язык: Английский

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MicroRNA-486-3p affects cisplatin resistance in high-grade serous ovarian cancer by regulating TMIGD2: An experimental study

Heliyon, Год журнала: 2024, Номер 10(15), С. e34978 - e34978

Опубликована: Июль 20, 2024

Язык: Английский

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Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(9), С. 10218 - 10248

Опубликована: Сен. 15, 2024

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate expression of SEMA7A, SEMA4D, ADAM8, ADAMTS10 colorectal (CRC) relation mutational landscape KRAS, NRAS, BRAF, PIK3CA, AKT genes, microsatellite instability (MSI) status, clinicopathological features. We also examined associations between these proteins selected cytokines, chemokines, growth factors, assessed using a multiplex assay. Protein concentrations were quantified ELISA CRC tumors tumor-free surgical margin tissue homogenates. Gene mutations evaluated via RT-PCR, MSI status was determined immunohistochemistry (IHC). GSEA statistical analyses performed R Studio. observed significantly elevated SEMA7A BRAF-mutant an overexpression ADAM8 KRAS 12/13-mutant tumors. The decreased PIK3CA-mutant No significant differences based on status. SEMA4D expressions correlated with numerous cytokines associated immune processes. potential immunomodulatory functions molecules their suitability as therapeutic targets require further investigation.

Язык: Английский

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Population genomics and transcriptomics identify patterns of selection in two Liangshan chicken breeds

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 6, 2024

Abstract The global diversity of domestic chicken breeds or lines, each exhibiting unique and specialized traits, offers a compelling context to explore how selection influences genetic variation patterns. China, with its myriad local breeds, contributes significantly this diversity. This study presents population genome overview variations in 35 chickens encompassing two distinct from the Liangshan Prefecture Sichuan Province. Through comparative genomic analysis 17 red jungle fowls (RJFs), genes associated natural Yanying Luning Chickens were identified. Notably, selected primarily affect energy metabolism, body size maintenance, available food sources, mirroring similar trends Chickens. Transcriptomic further validated potential roles these domestication both breeds. research sheds light on evolutionary trajectories shaped by artificial for agricultural purposes high-altitude chickens. identified specific as candidates influencing economic traits other phenotypic characteristics

Язык: Английский

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The level of cytokines in tears as a novel indicator of demyelinating diseases

Neurological Research, Год журнала: 2024, Номер 46(6), С. 487 - 494

Опубликована: Апрель 11, 2024

A novel research objective is to identify new molecules in more readily accessible biological fluids that could be used the diagnosis of multiple sclerosis (MS) and other demyelinating disorders.

Язык: Английский

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HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

World Journal of Surgical Oncology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 18, 2024

Abstract Background Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions HHLA2 pancreatic cancer (PC) remain incompletely elucidated. Methods We initially conducted an analysis family members’ pattern tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR western blot methods were used to assess levels PC cell lines. Furthermore, after silencing lines, migration proliferation cells detected by wound healing CCK-8 assays, invasion was transwell assays. also investigated regulation epithelial-mesenchymal transition (EMT) markers EGFR, MEK, ERK1/2, mTOR AKT via analysis. Finally, correlation between immune infiltration further explored. Results Silencing resulted inhibition proliferation, invasion, potentially through suppression EGFR/MAPK/ERK mTOR/AKT signaling pathway. Additionally, led M2-type polarization associated macrophages (TAMs). Conclusion knockdown observed inhibit EMT process found modulate M2 TAMs. These finding suggest that could be promising therapeutic target for Pancreatic cancer.

Язык: Английский

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