Recent Advancements, Limitations, and Future Perspectives of the use of Personalized Medicine in Treatment of Colon Cancer

Technology in Cancer Research & Treatment, Год журнала: 2023, Номер 22

Опубликована: Янв. 1, 2023

Due to the heterogeneity of colon cancer, surgery, chemotherapy, and radiation are ineffective in all cases. The genomic profile biomarkers associated with process considered personalized medicine, along patient's personal history. It is based on response targeted therapies specific genetic variations. transcriptomic epigenetic features evaluated, best therapeutic approach diagnostic testing identified through medicine. This review aims summarize necessary, updated information cancer related Personalized medicine gaining prominence as generalized treatments finding it challenging contain cases which currently rank fourth among global incidence while being fifth largest total death worldwide. In therapy, patients grouped into categories, chosen evaluating their molecular features. Various strategies explored treatment involving immunotherapy, phytochemicals, other biomarker-specific therapies. However, significant challenges must be overcome integrate healthcare systems completely. We look at various signaling pathways alterations understand identify useful therapy. current available improve existing methods discussed. highlights advantages limitations scenario developed countries faced middle- low-income also summarized. Finally, we discuss future perspectives how could integrated systems.

Язык: Английский

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The tumor microenvironment and dendritic cells: Developers of pioneering strategies in colorectal cancer immunotherapy?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер 1880(2), С. 189281 - 189281

Опубликована: Фев. 8, 2025

Язык: Английский

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PCSK9 facilitates melanoma pathogenesis via a network regulating tumor immunity

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Янв. 2, 2023

PCSK9 regulates cholesterol homeostasis and promotes tumorigenesis. However, the relevance of these two actions mechanisms underlying PCSK9's oncogenic roles in melanoma other cancers remain unclear.PCSK9's association with was analysed using TCGA dataset. Empty vector (EV), PCSK9, gain-of-function (D374Y), loss-of-function (Q152H) mutant were stably-expressed murine B16 cells studied for impact on cell-derived oncogenesis vitro vivo syngeneic C57BL/6 Pcsk9-/- mice. Intratumoral accumulation determined. RNA-seq performed individual tumor types. Differentially-expressed genes (DEGs) derived from comparisons D374Y, or Q152H tumors to EV allografts pathway alterations.PCSK9 expression its network negatively correlated survival probability patients melanoma. promoted cell proliferation, migration, growth soft agar vitro, formation mice vivo, intratumoral a manner reflecting regulation low-density lipoprotein receptor (LDLR): Q152H, EV, D374Y. Tumor-associated T cells, CD8 + NK significantly increased D374Y along upregulations multiple immune checkpoints, IFNγ, 143 associated dysfunction. Overlap 36 between DEGs predicted poor prognosis resistance checkpoint blockade (ICB) therapy. CYTH4, DENND1C, AOAH, TBC1D10C, EPSTI1, GIMAP7, FASL (FAS ligand) novel predictors ICB therapy displayed high level correlations checkpoints across 30 human cancers. We observed FAS ligand being among most robust biomarkers treatment constructed effective multigene panels predicting response The profiles produced by remained comparable mice.Tumor-derived plays critical role pathogenesis. are accumulation. systemically affects system, contributing evasion. Novel PCSK9-network effectively responses.

Язык: Английский

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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9463 - 9463

Опубликована: Авг. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Язык: Английский

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Signaling pathways in colorectal cancer implications for the target therapies

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Июнь 7, 2024

Abstract Colorectal carcinoma (CRC) stands as a pressing global health issue, marked by the unbridled proliferation of immature cells influenced multifaceted internal and external factors. Numerous studies have explored intricate mechanisms tumorigenesis in CRC, with primary emphasis on signaling pathways, particularly those associated growth factors chemokines. However, sheer diversity molecular targets introduces complexity into selection targeted therapies, posing significant challenge achieving treatment precision. The quest for an effective CRC is further complicated absence pathological insights mutations or alterations occurring tumor cells. This study reveals transfer from cell membrane to nucleus, unveiling recent advancements this crucial cellular process. By shedding light novel dimension, research enhances our understanding intricacies underlying providing potential avenue breakthroughs therapeutic strategies. In addition, comprehensively outlines immune responses incited aberrant activation specific focus cells, cytokines, their collective impact dynamic landscape drug development. not only contributes significantly advancing medicine but also lays groundwork future clinical trials, fostering optimism improved outcomes refined approaches combating colorectal carcinoma.

Язык: Английский

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The role of immunotherapy in microsatellites stable metastatic colorectal cancer: state of the art and future perspectives

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Май 3, 2023

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, despite several advances has been achieved in last decades. Few prognostic and predictive biomarkers guide therapeutic choice metastatic CRC (mCRC), among which DNA mismatch repair deficiency and/or microsatellite instability (dMMR/MSI) holds a crucial role. Tumors characterized by dMMR/MSI benefit from immune checkpoint inhibitors. However, most mCRC patients (around 95%) are stable (MSS), thereby intrinsically resistant to immunotherapy. This represents clear unmet need for more effective treatments this population patients. In review, we aim analyze immune-resistance mechanisms strategies overcome them, such as combinations immunotherapy chemotherapy, radiotherapy or target therapies specifically MSS mCRC. We also explored both available potential that may better select Lastly, provide brief overview on future perspectives field, gut microbiome its role immunomodulator.

Язык: Английский

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Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5876 - 5876

Опубликована: Март 20, 2023

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape HHLA2-related pathways in using available online datasets were analyzed. included 167 patients diagnosed with CRC. Expression of was detected by immunohistochemistry method (IHC) enzyme-linked immunosorbent assay (ELISA). IHC used evaluate MSI status. budding TILs measured a light microscope. concentrations molecules analyze data Bio-Plex Pro Human cytokine screening panel, 48 assay, principal component analysis (PCA). Geneset enrichment (GSEA) conducted identify pathways. biological function predicted Gene Ontology (GO). Analysis made web-based tool Camoip. High expression CRC tumor tissues compared adjacent noncancerous tissues. percentage HHLA2-positive tumors 97%. GSEA GO showed that upregulation correlated cancer-related several functions. Tumor-infiltrating score positively level percentage. There negative correlation HHLA2, anti-tumor cytokines pro-tumor growth factors. This provides valuable insight into role We reveal as well stimulatory inhibitory checkpoint cancer. Further research may verify therapeutic values HHLA2-KIR3DL3/TMIGD2 pathway

Язык: Английский

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PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials

BMC Cancer, Год журнала: 2023, Номер 23(1)

Опубликована: Ноя. 29, 2023

Abstract Background Paclitaxel and carboplatin is the standard chemotherapy for treatment of advanced or recurrent endometrial cancer. However, benefit adding programmed cell death 1 (PD-1)/programmed ligand (PD-L1) inhibitors to still unclear. Method We searched PubMed, Scopus, Cochrane, Web Science databases randomized controlled trials that investigated PD-1/PD-L1 plus paclitaxel compared with in primary computed hazard ratios (HRs) risk (RRs) binary endpoints, 95% confidence intervals (CIs). used DerSimonian Laird random-effect models all endpoints. Heterogeneity was assessed using I 2 statistics. R, version 4.2.3, statistical analyses. Results A total three studies 1,431 patients were included. Compared paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; CI 0.23–0.44; p < 0.001) overall (OS) at 30 months (RR 3.13; 1.26–7.78; = 0.01) significant favor group mismatch repair–deficient subgroup. there no differences repair–proficient subgroup PFS 0.74; 0.50–1.08; 0.117) OS 2.24; 0.79–6.39; 0.13). Conclusion Immunotherapy carboplatin-paclitaxel increased significantly among cancer, a high microsatellite instability population.

Язык: Английский

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Distant antimetastatic effect of enterotropic colon cancer–derived α4β7 ⁺ CD8 ⁺ T cells

Science Immunology, Год журнала: 2023, Номер 8(84)

Опубликована: Июнь 8, 2023

Despite the high prognostic value of immune infiltrates in colorectal cancer (CRC), metastatic disease remains resistant to immunotherapy by checkpoint blockade (ICB). Here, we show, CRC preclinical models, that orthotopically implanted primary colon tumors exert a colon-specific antimetastatic effect on distant hepatic lesions. Enterotropic α4β7 integrin–expressing neoantigen-specific CD8 T cells were key components effect. Accordingly, presence concomitant improved control liver lesions anti–PD-L1 proof-of-concept and generated protective memory, whereas partial depletion + abrogated metastases. Last, patients with CRC, response ICB was associated expression integrin metastases circulating cells. Our findings identify systemic immunosurveillance role for gut-primed tumor-specific

Язык: Английский

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Biomarkers in Metastatic Colorectal Cancer: Status Quo and Future Perspective

Cancers, Год журнала: 2022, Номер 14(19), С. 4828 - 4828

Опубликована: Окт. 3, 2022

Colorectal cancer (CRC) is the third most frequent worldwide, and its incidence steadily increasing. During last two decades, a tremendous improvement in outcome has been achieved, mainly due to introduction of novel drugs, targeted treatment, immune checkpoint inhibitors (CPIs) biomarker-driven patient selection. Moreover, progress molecular diagnostics but also surgical techniques local ablative treatments significantly contributed this success. However, therapeutic approaches are needed further improve patients diagnosed with metastatic CRC. Besides established biomarkers for mCRC, such as microsatellite instability (MSI) or mismatch repair deficiency (dMMR), RAS/BRAF, sidedness HER2 amplification, new have be identified better select who derive benefit from specific treatment. In review, we provide an overview about relevant shed light on potential promising markers that may help us tailor therapy individual mCRC near future.

Язык: Английский

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