CRC Warriors Scientific News

Últimas investigaciones científicas sobre cáncer colorrectal

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Targeting AVEN Liquid-Liquid Phase Separation in Colorectal Cancer: Insights From a Raddeanin A-Based Chemical Probe.

Mitochondrial dysfunction is a pivotal pathogenic mechanism in colorectal cancer (CRC), which is further exacerbated by dysregulated liquid-liquid phase separation (LLPS). However, the mechanisms underlying mitochondrial dysfunction and LLPS, as well as their therapeutic targeting, remain unclear. U...

Consensus Molecular Subtypes Inform HIPEC Agent Selection in Colorectal Cancer Peritoneal Metastases.

Although hyperthermic intraperitoneal chemotherapy (HIPEC) added to cytoreductive surgery shows promise for colorectal cancer with peritoneal metastases (CRC-PM), effectiveness remains variable. Given the predominance of consensus molecular subtype 4 (CMS4) in CRC-PM and resistance to standard agent...

The Prognostic Role of Postoperative Inflammation After Minimally Invasive Resection for Colorectal Cancer.

The relationship between inflammation and tumorigenesis has been widely investigated, with tumor-promoting inflammation proposed as an "enabling characteristic." However, little is known about the prognostic value of surgery-related inflammation. This study evaluates whether postoperative inflammati...

Functional vasculature in tumor organoids: Enabling precision medicine in oncology.

Conventional in vitro models often inadequately replicate the intricate vascular networks of tumors, limiting their translational relevance. Recent advances in vascularized tumor organoids offer a transformative approach to modeling angiogenic mechanisms and tumor microenvironment (TME) dynamics wit...

Tissue and Blood-Based Tumor Mutational Burden Predicts Treatment Response to PD-1 Blockade in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Tumor mutational burden (TMB) is a predictive biomarker for immune checkpoint inhibitors (ICIs). Its clinical utility in head and neck squamous cell carcinoma (HNSCC) is limited by differences in detection approaches and inconsistent cut-off values. In this meta-analysis, we systematically reviewed ...

Overcoming conditional immune resistance in MSS and pMMR colorectal cancer: A sequential gating framework for immunotherapy.

Microsatellite stable and mismatch repair proficient colorectal cancer (CRC) represents the largest population of patients exposed to immune checkpoint inhibitors, yet remains largely refractory to these therapies. Resistance is commonly attributed to low tumor mutational burden or limited neoantige...

Vitamin D receptor in tumors: A review of biological mechanisms, therapeutic potentials, and prognostic values.

The vitamin D receptor (VDR) is a key regulator of cellular growth and differentiation, and accumulating evidence links vitamin D signaling to tumor biology. However, the specific contributions of VDR across diverse cancers remain incompletely understood. This narrative review synthesizes current kn...

Ferroptosis in colorectal cancer: Molecular mechanisms and regulatory crosstalk with therapeutic prospects (Review).

Colorectal cancer (CRC) is a common malignancy of the colonic and rectal epithelia. Numerous patients with CRC derive only limited and unsustained benefit from conventional chemotherapy or immunotherapy, underscoring the need for novel treatments. Ferroptosis is an iron‑dependent, lipid peroxidati...

Adjuvant chemoradiotherapy versus completion total mesorectal excision after local excision for early rectal cancer (TESAR): a multicentre, randomised, controlled, phase 3, non-inferiority trial.

Completion total mesorectal excision (cTME) after local excision of early rectal cancer is associated with substantial morbidity and impaired functional outcomes. This study aimed to assess the oncological outcomes of adjuvant chemoradiotherapy as an organ-preserving alternative in patients with hig...

Neferine-enhanced Shenling Baizhu Tang potentiates anti-PD-1 therapy in colorectal cancer liver metastasis via CYP2E1-PPARα-mediated lipid reprogramming.

Immune checkpoint inhibitors elicit responses in merely 20-40% of patients with microsatellite instability-high or mismatch repair-deficient colorectal cancer (CRC), making immunotherapy resistance a formidable clinical challenge. The immunosuppressive tumor microenvironment, characterized by regula...

Functional precision oncology platform of BRAF(V600E)-mutated colorectal cancer organoids predicts therapy response and reveals RNF43-mediated immunogenicity.

BRAFV600E-mutant colorectal cancer (CRC) represents an aggressive molecular subtype characterized by poor prognosis and resistance to standard therapies. Predictive models to guide treatment selection and overcome drug resistance are urgently needed. We established a biobank of patient-derived organ...

Evaluation of ct-DNA and mutational status in liquid biopsy of patients with metastatic colorectal cancer.

Liquid biopsy has become an increasingly important tool in clinical oncology due to the utility of circulating tumor DNA (ct-DNA). Plasma ct-DNA levels reflect the tumor burden of patients and provide valuable information for personalized treatment strategies. Colorectal cancer (CRC) is among the mo...

Peptide-drug conjugates bearing an antimitotic Ahx-DA1 payload achieve potent antitumor activity in Her2-amplified and EGFR-positive KRAS-mutant cancers in vivo.

Peptide-drug conjugates (PDCs) represent a targeted cancer therapy strategy that combines tumor-homing peptides with potent cytotoxic payloads, offering a promising alternative to antibody-drug conjugates (ADCs) through improved tissue penetration, synthetic accessibility, and tumor selectivity. Aur...

ASO Visual Abstract: Combined RAS and SMAD4 Mutations and Microsatellite Instability Predict Outcomes in Colorectal Lung Metastases Treated with Image-Guided Thermal Ablation.

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Combined RAS and SMAD4 Mutations and Microsatellite Instability Predict Outcomes in Colorectal Lung Metastases Treated with Image-Guided Thermal Ablation.

Image-guided thermal ablation (IGTA) is a minimally invasive alternative to colorectal cancer lung metastases (CRLM) for non-surgical candidates. This study evaluated whether combined RAS/SMAD4 mutational status and microsatellite instability (MSI) predict outcomes after IGTA in CRLM, addressing the...

Dysplasia in sessile serrated lesions: frequency, interobserver variability and added value of immunohistochemistry.

Sessile serrated lesions with dysplasia (SSLd) are direct precursors of colorectal carcinomas (CRCs) but pose a diagnostic challenge. We aim to explore contemporary practice leading to recommendations to improve detection of dysplasia. (i) The frequency of dysplasia in SSLs was estimated through a n...

Methionine-depleting engineered probiotics promote PD-L1 antibody immunotherapy by activating the STING pathway.

The metabolic differences between tumor cells and normal tissue cells offer potential targets for therapeutic intervention. For instance, compared to normal tissues, tumor cells exhibit a significantly higher dependency on methionine. However, current strategies for methionine restriction have limit...

Harnessing biomimetic nano-regulators for in situ photothermia and lactate regulation to amplify cuproptosis immunotherapy.

Cuproptosis represents a promising avenue for cancer immunotherapy, yet its efficacy is limited by difficulties in achieving targeted mitochondrial copper ion accumulation and upregulating cells reliance on mitochondrial respiration. To address this, we develop a biomimetic copper-based nanoplatform...

Chemoimmunotherapy enables adaptive strategies in locally advanced MSS colorectal cancer.

Early exposure to checkpoint blockade restores immune-sensitivity in localized, immune-excluded cancers. In this issue of Med, Zhang et al. reported promising pathological activity of 3-month preoperative cadonilimab (bispecific anti-PD-1/CTLA-4 antibody) with modified FOLFOXIRI triplet intensive ch...

Dual CTLA-4/PD-1 Blockade Versus Anti-PD-1 in MSI-H Metastatic Colorectal Cancer: Early Survival Benefit and Exploratory Clinical Predictors.

Immune checkpoint inhibitors (ICI) are standard for MSI-H/dMMR metastatic colorectal cancer (mCRC). We compared their efficacy and sought subgroups deriving greater benefit from ICI combination. All patients with MSI/dMMR mCRC treated by anti-PD-1 ± anti-CTLA-4 in the prospective monocenter immunoM...

Enhancing Immunotherapeutic Response in Colorectal Cancer with a Neuropilin 1-Targeting Tumor-Penetrating Peptide.

Immune checkpoint inhibitors (ICI) provide durable responses in a subset of colorectal cancers, yet benefit is largely confined to microsatellite instability-high (MSI-H) tumors. We investigated whether the tumor-penetrating peptide iRGD enhances anti-programmed cell death protein 1 (PD-1) treatment...

BRAF-targeted therapy in non-melanomatous BRAF-mutant tumours: a systematic review of broad but histology-modulated efficacy.

Tumour agnostic therapies represent a paradigm shift in oncology. BRAF inhibitors have demonstrated efficacy in melanoma. However, their role in non-melanomatous cancers was originally contentious. This systematic review aims to evaluate the safety and efficacy of BRAF-targeted therapies, both as mo...

Beclin-1 as an autophagy biomarker in colorectal cancer.

Colorectal cancer (CRC) is the leading cause of cancer-related morbidity and mortality attributable to cancer worldwide. Therefore, there is still a need for strong biomarkers that can be used to assist with the diagnosis, prognostication, and therapeutic stratification of patients. The role of auto...

Emerging biomarkers for early detection of colorectal cancer.

The worldwide impact of colorectal cancer (CRC) as a primary cause of cancer-related morbidity and mortality demonstrates the urgent need for better early detection methods and personalized treatment approaches. While colonoscopy and fecal tests have contributed to reduced mortality rates from CRC, ...

Association Between ABO Blood Group and Survival in Early-Stage Colon Cancer: A Single-Center Retrospective Cohort Analysis.

ABO blood group antigens influence cell adhesion, inflammation, and metastatic processes, raising interest in their potential prognostic role in colorectal cancer. However, previous studies have reported inconsistent findings. This study evaluated the association between ABO blood group and overall ...

Site-dependent Treg cell transcriptional reprograming in a metastatic colorectal cancer model holds prognostic significance.

In colorectal cancer (CRC), tumor-infiltrating regulatory T (Treg) cells suppress anti-tumor immunity, promoting immune evasion and tumor progression. Effective therapies require selectively targeting tumor-infiltrating Treg (TI-Treg) cells while preserving systemic Treg cells, necessitating insight...

Discovery of a novel and potent KRAS(G12V)-targeting peptide with antiproliferative activity against colorectal cancer cells.

Despite the clinical relevance of KRASG12V in colorectal cancer, KRASG12V-specific inhibitors remain limited. Through structure-based virtual screening of a 59,319-member peptide library, we identified four KRASG12V-targeting peptides, among which Peptide-1 showed the most favourable docking profile...

Clinical factors are more strongly associated with prognosis than genetic alterations in early-onset colorectal cancer: a retrospective cohort study.

Early-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical and genetic factors to prognosis remains unclear, particularly in underrepresented populations...

Dual mechanism of immune escape shapes the genetic and immunogenic landscape of mismatch repair-deficient colorectal tumours.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) are highly mutated and immunogenic yet frequently escape immune elimination. To define how host immunity shapes the genomic architecture and tumour microenvironment of MMRd CRC. We used a genetically engineered mouse model of MMRd CRC to com...

Sanwu Huangqin decoction induces ferroptosis in colorectal cancer cells by triggering NCOA4/FTH1-mediated ferritinophagy.

In traditional Chinese medicine (TCM), colorectal cancer (CRC) is commonly associated with patterns such as damp-heat accumulation, heat toxin, and yin deficiency. Sanwu Huangqin Decoction (SWHQD) is a classical traditional Chinese medicine (TCM) formula composed of three medicinal herbs-Huangqin (S...

Predictive Biomarkers in Metastatic Colorectal Cancer Patients Treated With Bevacizumab: A Turkish Oncology Group (TOG) Study.

Efforts to improve outcomes for patients with metastatic colorectal cancer (mCRC) treated with bevacizumab are limited by the lack of validated predictive biomarkers. To overcome this challenge, our study prospectively assessed the combined prognostic and predictive significance of circulating angio...

Targeting Ferroptosis to Overcome Radioresistance and Enhance Immunotherapy in Colorectal Cancer.

Locally advanced rectal cancer is commonly treated using total neoadjuvant therapy (TNT), which integrates radiotherapy with systemic chemotherapy to improve tumor downstaging, local control, and long-term oncologic outcomes. Despite its central role in treatment, responses to radiotherapy remain hi...

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer.

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerizat...

Exploring Risk Factors and Sex Differences in Colorectal Cancer: Insights from Current Evidence.

Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. A consistent and epidemiologically well-documented feature of CRC is its sexual dimorphism: age-standardized incidence rates are 33-45% higher in men than in women, and ...

VEGFR2-targeted NIR-II fluorescent probe for precise imaging and surgical navigation of ovarian cancer.

Molecular imaging of tumor biomarkers represents a crucial direction for advancing precision cancer diagnosis and therapy. As a core regulator of tumor angiogenesis, VEGFR2 represents an ideal molecular imaging target. Herein, a novel VEGFR2-targeting peptide (HTMYYHHYQHHLSSSDICLPRWGCLWED, named as ...

TME/NIR Dual-Responsive Zinc-Based Targeted Nanoagonist for Multimodal Amplification of STING-Mediated Cancer Immunotherapy.

The precise activation of the cGAS-STING pathway for effective tumor immunotherapy remains a significant challenge due to the complexity of immune responses and tumor microenvironment (TME) limitations. Here, a multifunctional nanoagonist, cRGD-PDA/ZIF8@ICG/TPT (cDZ@IP), was developed to realize nan...

TIMEL: Deep learning-statistical integration reveals spatial stromal and immune signatures of aggressive colon cancer.

Characterizing the tumor immune microenvironment (TIME) is essential for understanding anti-tumoral responses in colon cancer. This study introduces TIME Landscaper (TIMEL), a computational framework that uses deep learning to identify tissue structures at the microscopic level and summarizes their ...

Lidocaine enhances antitumor effects of sorafenib and GW5074 in colorectal cancer cells.

Targeted therapies have broadened the treatment landscape for colorectal cancer (CRC), highlighting the need for rational combination strategies. Although sorafenib and GW5074 show therapeutic promise and lidocaine may sensitise cancer cells to treatment, the mechanisms underlying these combinations...

Combining the KRAS(G12C) inhibitor adagrasib with anti-PD-1 immunotherapy improves overall survival and prevents recurrence in preclinical models of brain metastasis.

Despite advances in treatment, brain metastasis (BM) management remains a significant challenge. Adagrasib is a brain-penetrant KRASG12C inhibitor active in patients with BM. KRAS mutations are linked with immune escape and may contribute to the limited clinical benefit from single-agent immune chec...

Injectable anaerobic hydrogel loading Clostridium butyricum for local hydrogen therapy against colorectal cancer.

Hydrogen (H2), a non-toxic therapeutic gas, exerts antitumor effects by disrupting intracellular redox homeostasis and inducing mitochondrial dysfunction. The high diffusibility of H2, as well as its storage difficulties, hinders its sustained release at tumor sites. Thus, the therapeutic effect rem...

The prognostic significance of B7-H3 expression in patients with advanced colorectal cancer.

Biomarkers, particularly prognostic and immune based, are lacking in colorectal cancer (CRC). This study aimed to evaluate the expression of novel immune based biomarkers among patients with CRC to predict clinical outcomes. A CRC tumor microarray (TMA) was developed from a multiracial patient popul...

Absence of co-occurrence between HER2 amplification and dMMR/MSI in a large multicentric colorectal cancer cohort.

Mismatch repair deficiency (dMMR)/Microsatellite instability (MSI) plays a central role in colorectal cancer (CRC) as a predictive and prognostic biomarker and as a "red flag" for diagnosis of Lynch Syndrome (LS). HER2 is emerging as a therapeutic target and clinical trials are ongoing. Several repo...

Impact of medical oncologist certification on survival outcomes in metastatic colorectal cancer: evidence from the SCRUM-Japan MONSTAR-SCREEN Observational Study.

Board certification in surgical oncology improves cancer outcomes, but the impact of medical oncologist certification on systemic therapy outcomes is unknown. We investigated whether the Japanese Society of Medical Oncology (JSMO) board certification of the enrolling physician was associated with tr...

Executive summary of American Radium Society Appropriate Use Criteria for the treatment of locoregionally recurrent rectal cancer.

This literature-based systematic review and associated guidelines provide evidence-based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal ...

Successful Management of BRAF V600E-Mutated Metastatic Colorectal Cancer With Liver Dysfunction Using Encorafenib-Based Therapy.

The recent approval of encorafenib, cetuximab, and FOLFOX based on the phase III BREAKWATER trial has introduced a new standard of care for the first-line treatment of BRAF V600E-mutated metastatic colorectal cancer (mCRC). However, its safety and efficacy in patients with significant liver dysfunct...

[Personalized pharmacotherapy of colorectal cancer].

Treatment of colorectal cancer has fundamentally evolved due to molecular characterization and biomarker-driven strategies. To summarize key personalized treatment approaches in colorectal cancer with a focus on clinically relevant molecular subgroups. Molecular biomarkers increasingly guide treatm...

Development and in vivo evaluation of (18)F-labeled PET tracers covalently targeting KRAS-G12C for noninvasive cancer diagnosis and therapy monitoring.

Mutations in the KRAS gene are some of the most frequent drivers in cancer, including non-small cell lung and colorectal cancer. Covalent inhibitors such as adagrasib, targeting the inactive, GDP-bound form of KRAS-G12C, have shown clinical efficacy but patient selection still depends on invasive bi...

From dose to exposure? rethinking fluoropyrimidines as immune checkpoint partners in gastrointestinal cancers.

Fluoropyrimidine regimens in gastrointestinal oncology have evolved empirically. Bolus 5-fluorouracil (5-FU)-containing combinations now coexist with continuous metronomic schedules and oral prodrugs, while immune checkpoint inhibitors (ICIs) seek chemotherapy partners for microsatellite-stable (MSS...

Guanylyl Cyclase 2C-Targeted Chimeric Antigen Receptor T-Cell Therapy in Patients With Metastatic Colorectal Cancer.

The clinical efficacies of third- or later-line therapies for metastatic colorectal cancer (CRC) are extremely limited. The purpose of this study was to evaluate the safety and efficacy of a chimeric antigen receptor T (CAR T) cell targeting guanylyl cyclase 2C (GUCY2C) that was steadily expressed i...

Beyond Sidedness: DNA Methylation as a Biomarker to Refine Anti-EGFR Treatment Selection in RAS/BRAF Wild-type Metastatic Colorectal Cancer.

Primary tumor sidedness is a major determinant of biologic-agent selection in RAS/BRAF wild-type metastatic colorectal cancer (mCRC), but it remains an anatomic surrogate rather than a mechanistic biomarker. Genome-wide DNA methylation status has emerged as a biologically informative classifier that...

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