Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: A review

Medicine, Journal Year: 2024, Volume and Issue: 103(2), P. e36957 - e36957

Published: Jan. 12, 2024

Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as transformative approach, leveraging the body immune system against cancer, including checkpoint inhibitors (ICIs), cancer vaccines, adoptive cell transfer. These modalities shown promise, achieving sustained responses improved survival some patients. However, their efficacy GI is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines latest understanding of immunotherapy cancers, focusing on ICIs, transfer, along with associated outcomes limitations. It delves into behind resistance, alterations checkpoints, immunosuppressive tumor microenvironment, genetic/epigenetic changes. The role gut microbiome also considered an emerging factor resistance. To combat strategies such enhancing response, targeting modulating explored. underscores potential ferroptosis induction novel approach. Looking forward, it highlights need personalized immunotherapies, influence microbiome, further exploration overcoming challenges persist, continuous evolution research promises innovative could significantly improve patient outcomes.

Language: Английский

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Circulating miRNA and circulating tumor DNA application as liquid biopsy markers in gastric cancer

Clinical Biochemistry, Journal Year: 2024, Volume and Issue: 129, P. 110767 - 110767

Published: May 4, 2024

Language: Английский

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Integrated clinico-molecular analysis of gastric cancer in European and Latin American populations: LEGACY project

ESMO Open, Journal Year: 2025, Volume and Issue: 10(3), P. 104482 - 104482

Published: March 1, 2025

Gastric cancer (GC) is recognized for intrinsic heterogeneity, although it similarly approached in Europe and Latin America (LATAM). The LEGACY project aimed to deepen GC molecular understanding through multi-omics analysis LATAM samples. Tumor samples were centrally reviewed histology, human epidermal growth factor receptor 2 (HER2) expression, mismatch repair-deficient (dMMR)/microsatellite instability (MSI) status. In addition, we assessed Epstein-Barr virus (EBV) status, programmed death-ligand 1 (PD-L1) combined positive score (CPS), carried out tissue genomic profiling including tumor mutation burden (TMB) quantification plus targeted transcriptomics immune microenvironment cell signaling scores. total, 328 patients enrolled. HER2-positive high PD-L1 CPS more frequent than (9% versus 3% 15% 3%, respectively), whereas EBV was mainly found (7%, Europe), dMMR/MSI tumors equally distributed (16%). High TMB enriched tumors. Mutations homologous recombination repair (HRR) genes both cohorts (24.8% 14.7% LATAM, mostly (63.6%) intestinal HER2-negative (18.7%) prognosis poor diffuse patients, whose presented an immunosuppressive other distinct pathway activation signatures. Our findings relate specific alterations of from actionable biomarkers precision therapies. proposed stratification can be implemented routine care guide drug development strategies.

Language: Английский

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Bile as a liquid biopsy matrix: potential applications and limitations

Published: Feb. 4, 2024

Hunting for tumoral material in body fluids, traditionally blood, the so-called liquid biopsy is set to revolutionize diagnosis and management of oncological patients. However, other biofluids can also be considered as alternative sources biomarkers provide clinically valuable information multiple diseases. This case bile, a fluid produced liver, stored gallbladder, excreted duodenum, which complex composition known change different pathological conditions. Remarkably, works have demonstrated that identification mutations bile cell-free DNA (cfDNA) outperform blood analysis early biliopancreatic tumors causing biliary strictures. Here, literature has been tested matrix where lipids, metabolites, proteins, cfDNA among analytes were measured reviewed. Moreover, clinical situations procedures available, discussing possible applications limitations are summarized. The scientific relevance potential harvesting, biobanking, put forward. All this evidence supports value patients beyond cancer, perhaps “blood, sweat, tears”.

Language: Английский

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Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 13, 2024

Abstract Pancreatic ductal adenocarcinoma represents one of the solid tumors showing worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as promising non-invasive tool to characterize genomics and assess treatment response. In this study, surgical tissue sequential blood samples were analyzed by next-generation sequencing correlated clinical pathological characteristics. Thirty resectable/borderline pancreatic patients treated at Hospital Universitario de Navarra included. tumoral identified pathogenic variants in KRAS TP53, other cancer-associated genes. Pathogenic diagnosis detected poorer outcome, response therapy borderline adneocarcinoma patients. Higher variant allele frequency was associated worse prognosis, thesum greater progression. Our results build on potential value circulating for non-metastatic patients, complementing genetic information decision. Confirmatory studies are needed corroborate these findings.

Language: Английский

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A critical appraisal of the potential benefit of post-operative structured follow-up after resection for biliary tract cancer

HPB, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 1, 2023

Abstract

Background

There is currently no evidence to support structured use of imaging or biomarkers during follow-up patients after curative resection biliary tract cancer (BTC). Besides, the influence early detection recurrence and subsequent start palliative chemotherapy on overall survival remains unknown. The aim this study describe compare results two strategies.

Methods

This retrospective multicenter cohort compared from Amsterdam UMC undergoing pragmatic clinical follow-up, observational BILCAP follow-up. Primary outcome was survival.

Results

A total 315 were included n=91 pragmatic, n=224 follow-up). At median 56.9 months, 189 (60%) diagnosed with recurrence. After recurrence, more received (chemo) therapy in group (43% vs 75%, P<0.001). Median lower (27.7 39.1 P=0.003). who actually comparable (27.2 27.7 P=0.574).

Conclusion

describes Although these groups are biased, it noted that fewer but those had similar

Language: Английский

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Improving outcomes in patients with perihilar cholangiocarcinoma

Published: Feb. 4, 2024

The aim of this thesis was to investigate how improve outcomes in patients with perihilar cholangiocarcinoma (pCCA). To achieve this, several topics including resection margin, lymph node status, additional resection, preoperative (chemo) therapy and follow-up methods were covered. In Chapter 1, we gave an introduction on outcome pCCA. After imaging defining resectability, the first step towards optimal surgical treatment is optimizing biliary drainage preventing cholangitis, followed by securing adequate future liver remnant volume and/or function. main goal for pCCA achieving radical ultimately long-term survival. 2, described initially resectable who randomized between endoscopic (EBD) percutaneous (PTBD) DRAINAGE trial. This study demonstrates complexity potentially date, decision whether a patient seems based expert opinion decided consensus. Resectability actual resectability determined during exploration. Unfortunately, 10 30 % turns out have unresectable disease exploration due more extensive than expected imaging. Preoperative chemotherapy may downstage convert tumors resectable. However, order allocate best possible treatment, (e.g. therapy, or palliative therapy) universal, widely implemented, reproducible criteria are needed. Therefore using modified Delphi method, Thirteen HPB-surgeons, from six tertiary referral centers Netherlands, presented 3. 4, systematic literature review described. aimed efficacy safety systemic induction locally advanced intrahepatic (iCCA) summarized used across these studies. 5, retrospective cohort potential gemcitabine cisplatin as borderline iCCA, pCCA, mid-cholangiocarcinoma discussed. Unresectable recurrent treated consisting cisplatin. large variation response within exists. 6, investigated Human Equilibrative Nucleoside Transporter 1 (hENT1) biomarker. hENT1 considered predictive biomarker efficacy, its prognostic value however still under debate. Currently, benefits after positive proximal intraoperative frozen sections (IFS) residual oncological remain uncertain. Therefore, 7 retrospective, multicenter, matched case-control performed. Lymph metastasis margins been reported be major determinants overall survival poor recurrence-free 8 assess nodes margin status OS. There no evidence support structured use biomarkers curative tract cancer (BTC). could cause recurrence noticed earlier stage. Which ensure better performance patients, leading quick start prolonging 9 two strategies resected BTC investigated.

Language: Английский

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Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 2, 2024

Background. Pancreatic ductal adenocarcinoma (PDAC) represents one of the worst prognostic cancers worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy (NAT). Circulating tumor DNA (ctDNA) analysis raised as promising non-invasive tool to characterize genomics and assess treatment response.Methods. In this study, surgical tissue sequential blood samples were analyzed by next-generation sequencing correlated clinical pathological characteristics. Thirty resectable/borderline PDAC patients treated at Hospital Universitario de Navarra (HUN) included.Results. ctDNA identified pathogenic variants in KRAS TP53, other cancer-associated genes. Pathogenic diagnosis detected poorer outcome, response NAT borderline patients. Higher variant allele frequency (VAF) was associated worse prognosis, VAF sum greater progression.Conclusion. Our results build on potential value for non-metastatic patients, complementing genetic information decision. Confirmatory studies are needed corroborate these findings.

Language: Английский

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Current practices and challenges in implementing precision medicine for upper gastrointestinal cancers in European academic centers: an EORTC survey

ESMO Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 5, P. 100074 - 100074

Published: Aug. 8, 2024

Language: Английский

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