The ncRNA-TGF-β axis: Unveiling new frontiers in colorectal cancer research

Pathology - Research and Practice, Год журнала: 2024, Номер 254, С. 155138 - 155138

Опубликована: Янв. 14, 2024

Язык: Английский

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New approach in Understanding Colorectal Cancer Immunosuppression and Immunotherapy-Based Strategies in the Treatment of Microsatellite Stable Colorectal Cancer

Acta Medica Bulgarica, Год журнала: 2024, Номер 51(2), С. 65 - 72

Опубликована: Июнь 1, 2024

Abstract Except the widely accepted use of immune Checkpoint inhibitors in treatment microsatellite instability-high (MSI-H) mismatch repair-deficient (MMRd) CRCs representing about 5% all metastatic (m)CRC patients, new strategies are applied to cure MMR-proficient (MMRp) mCRC patients. Tumor microenvironment (TME) is decisive for cancer development. The determination some immunoeffective and immunosuppressive cells cytokines, chemokines growth factors TME gives Information MMRp CRCs. increased level IL-6 serum number IL-6+ TME, IL-17+ Th17 cells, FoxP3+ used determine anti-IL-6 antibody anti-FoxP3 treatment. high CD8+, PD-1 expression little or no appoint better response anti-PD-1 therapy. combination therapies are: immunotherapy with chemotherapy, radiation therapy, targeted vaccines, oncolytic viruses bispeeifie antibodies. Classical CRC patients has included radiotherapy surgery. Recently, been added as a mainstay therapy CRC. main checkpoint pembrolizumab nivolumab (anti-PD-1), durvalumab (anti-PD-L1), ipilimumab (anti-CTLA-4), favezelimab (anti-LAG3), etc. They after fluorapyrimidine, oxaliplain, irinotecan In conclusion, we may state that future MSS therapies, i.e. conventional immunotherapies. We consider infiltrate must be assessed order therapies.

Язык: Английский

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Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 18, 2024

Background A multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting efficacy immunotherapy use immune checkpoint inhibitors (ICIs). In light these findings, U.S. Food Drug Administration (FDA) has authorized several ICIs specific subpopulations mCRC patients. Nevertheless, there remains a dearth direct comparative RCTs evaluating various options. Consequently, most effective ICI therapeutic strategy microsatellite-stable (MSS) subgroup microsatellite instability (MSI) first- second-line therapies undefined. To address this gap, present study employs Bayesian network meta-analysis to ascertain strategies. Methods comprehensive literature search was across multiple databases, including PubMed, EMBASE, Cochrane Library, Web Science, retrieval date ranging from databases’ inception August 20, 2024. total 875 studies were identified, seven ultimately included analysis after screening process. systematic review on basis results. Results This analysis, comprising RCTs, evaluated first-line regimens 1,358 mCRC. The treatments under investigation consisted five treatments, three focusing MSS two MSI patients, as well secondary regimens, 1051 individuals underwent treatment, while 307 received treatment. application proved offer varying degrees benefits when compared standard-of-care therapy alone, subgroups first second phases. Of particular note is performance Nivolumab combination ipilimumab, which demonstrated superior improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, an optimal safety profile, relatively low risk adverse events (OR = 0.33; 0.19–0.56), other modalities subgroup. Regarding subgroup, improvement PFS by plus (SOC) significant (HR 0.74; 0.53-1.02). realm administration Atezolizumab SOC proven be approach prolonging PFS, exhibiting HR 0.66 (95% 0.44–0.99). These findings underscore profiles lines. Conclusions strategies yields substantial benefits. detailed assessment indicates that ipilimumab may represent efficacious well-tolerated terms therapy, relative choice. context it evident represents preferable option enhancing PFS. Furthermore, noteworthy also exhibit great value aspects, potential inform development future guidelines provide stronger rationale selection Systematic registration https://www.crd.york.ac.uk/prospero/#recordDetails , identifier CRD42024543400.

Язык: Английский

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Association of HLA-G 3′UTR Polymorphisms with Response to First-Line FOLFIRI Treatment in Metastatic Colorectal Cancer

Pharmaceutics, Год журнала: 2022, Номер 14(12), С. 2737 - 2737

Опубликована: Дек. 7, 2022

Microenvironmental factors such as non-classical human leukocyte antigen-G (HLA-G) have been associated with cancer invasiveness and metastatic progression. HLA-G expression has specific single-nucleotide polymorphisms (SNP) in 3'untranslated region (UTR) several diseases. The primary aim was to investigate the predictive role of on treatment efficacy colorectal (mCRC) patients homogeneously treated first-line FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) their association soluble (sHLA-G) plasma concentration. 3'UTR sequenced 248 patients. A set eight related haplotypes were analyzed for best tumor response, overall survival (OS), progression-free (PFS). sHLA-G measured by immunoassay 35 available samples correlated polymorphisms/haplotypes. Our results showed that carriers rs371194629 (+2960)-Ins allele at risk lack complete response (hazard ratio (HR):0.29, pBH = 0.0336), while rs1710 (+3010)-G (rs1063320 (+3142)-C linkage-disequilibrium), rs9380142 (+3187)-G had a higher chance according additive models (HR:4.58, 0.0245; HR:3.18, 0.0336, respectively). combination rs371194629-Del, rs1710-G, rs9380142-G alleles forms UTR1 haplotype. Patients who UTR1/UTR-1 diplotype greater therapy (HR:10.59, 0.0294). same three beneficial trend toward pre-treatment levels, supporting functional protein secretion. In conclusion, genetic variants are mCRC FOLFIRI. This finding shed light combined effect this immune system factor chemotherapy

Язык: Английский

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Promises and challenges for targeting the immunological players in the tumor micro-environment – Critical determinants for NP-based therapy

OpenNano, Год журнала: 2023, Номер 10, С. 100134 - 100134

Опубликована: Фев. 22, 2023

Immunotherapy holds great promises to address an effective and durable therapeutic response in a wider range of cancer types. However, the understanding complex immune biology interactions within Tumour Immune Microenvironment (TiME) is limited. This aspect, coupled with unmet challenges pertaining development testing drug delivery modes operations, has overall resulted large attrition rate few anti-cancer therapeutics reaching clinic. Also, thorough cellular features other components TiME terms spatial temporal heterogeneity cell types, stoichiometries, functional states will further aid expediting discovery process. Better evolving immunological players (TME), that dictate process evasion governed by tumours, present opportunities for targeted interventions, including those involving NP-based strategies. Moreover, more physiologically relevant models requires utilization ex vivo patient-specific materials or traditional line-based mono and/or heterotypic culture can recapitulate TiME. Such be used test potential candidates, NP (nanoparticle)-based constructs their targetability, deep tumor penetration as well pharmacological responses efficiently expeditiously. passage NP-drug conjugate through various anatomical pathological barriers, before it reaches its site action. One determinants affecting biodistribution, transport, uptake clearance involves dynamic protein corona (PC) around confers new "biological identity". Hence, PC should modelled using systems formation, evolution turnover, aside from employment analytical tools characterization. In summary, this review focuses on elucidation composition, advancements vitromodeling constitution, treatment strategies nanocarrier approaches counter adverse enhancement efficacy order improve clinical response.

Язык: Английский

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