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Últimas investigaciones científicas sobre cáncer colorrectal

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Surgery for bilobar colorectal liver metastasis: from staged resections to liver transplantation. A systematic review of the outcomes of the different strategies.

The management of multiple bilobar colorectal liver metastases (BCRLMs) continues to evolve, and the optimal strategy remains controversial. This was a systematic review that analyzed the outcomes of different surgical strategies for BCRLMs. A systematic literature search that included MEDLINE, Emba...

Compression-induced metabolic adaptation drives confined tumor cell migration and distant metastasis via malate-dependent microtubule reinforcement.

Metastasis, responsible for > 90% of cancer-related mortality, represents the most lethal yet least mechanistically understood phase of cancer progression. A critical bottleneck is tumor cell migration through physically confined environments, including dense extracellular matrix, narrow capillaries...

Safety and Efficacy of a Sandwich Total Neoadjuvant Therapy Strategy for Low-Risk Distal Locally Advanced Rectal Cancer: Results From the TESS Phase II Trial.

This prospective phase II multicenter study evaluated a novel sandwich total neoadjuvant treatment (TNT) strategy for patients with relatively low-risk distal locally advanced rectal cancer (LARC). The regimen consisted of two cycles of capecitabine and oxaliplatin (CapeOx) administrated before, dur...

Effect of one or two cycles of dual immunotherapy with nivolumab and ipilimumab in patients with mismatch repair-deficient rectal cancer (RESET-R): interim results from a multicentre, single-arm, phase 2 trial.

Mismatch repair-deficient (dMMR) tumours are highly sensitive to immune checkpoint blockade in the metastatic setting. Previous trials showed near-universal pathological responses after short-course dual immune checkpoint inhibition in patients with early-stage dMMR colon cancer, and high clinical c...

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...

Sotorasib plus panitumumab and 5-fluorouracil in first-line treatment of patients with unresectable KRAS G12C mutated colorectal cancer unfit for a doublet/triplet chemotherapy: ENGIC 01 - PRODIGE 107 - FFCD 2306 - COLOSOTO trial.

5-fluorouracil (5-FU) ± targeted therapy is a standard of care in frail/elderly patients with an unresectable colorectal adenocarcinoma (CRC) in first-line setting. Panitumumab plus sotorasib combination (KRAS G12C inhibitor) are promising in advanced line in KRAS G12C-mutated CRC. Here we assess t...

Prior response to anti-VEGF agents predicts the efficacy of trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer.

Trifluridine/Tipiracil (FTD/TPI) combined with bevacizumab (Bev) is a standard treatment for patients with unresectable metastatic colorectal cancer (mCRC) in later-line therapy. Despite the availability of other drugs like regorafenib and fruquintinib, there is no consensus on the optimal treatment...

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...

Next-Generation Sequencing-Based Analysis of the Genetic Mutation Spectrum in Colorectal Cancer: A Large Single‑Center Study From Southeast China With Cross‑Population Comparison.

Colorectal cancer (CRC) exhibits considerable molecular heterogeneity. This study aimed to delineate the mutational landscape and investigate the associations between frequently mutated genes and key clinicopathological features in a single-center cohort of CRC patients using next-generation sequenc...

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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RUNX1 Directly Activates WNT2 to Orchestrate Tumor-Associated Macrophage Reprogramming in Colorectal Cancer.

Tumor-associated macrophages (TAMs), particularly the M2 subtype, foster immune suppression and metastasis in colorectal cancer (CRC). Although WNT2 is upregulated in several cancers and RUNX1 is an oncogenic transcription factor in solid tumors, whether a RUNX1-WNT2 axis orchestrates M2 polarizatio...

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...

IRS2 as a driver and therapeutic target in brain metastases from colorectal cancer: a systematic review of mechanistic and translational evidence.

Brain metastases (BrM) from colorectal cancer (CRC) are rare but carry dismal prognosis. Emerging genomic analyses have identified insulin receptor substrate 2 (IRS2) amplification as a recurrent event in CRC BrM, suggesting a role in brain tropism and metabolic adaptation. To systematically evaluat...

Identification of the Lynch syndrome and Lynch-like syndrome specific somatic mutations in microsatellite instability-high colorectal cancer cases.

Lynch syndrome (LS), the most common hereditary colorectal cancer (CRC), is caused by germline mutations in mismatch repair (MMR) genes, resulting in microsatellite instability-high (MSI-H) tumors. Lynch-like syndrome (LL) exhibits MSI-H and MMR deficiency, but lacks identifiable germline MMR mutati...

Study protocol: targeted delivery of interleukin-12 in combination with hepatic artery infusion pump therapy for patients with adrenocortical carcinoma liver metastases.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy often detected at an advanced stage with limited effective treatment options beyond first-line chemotherapy. The liver is a common site of metastasis, and patients frequently present with substantial hepatic disease burden that preclude...

CAR T targets: AI takes the wheel.

Identifying safe and effective targets remains a major bottleneck for CAR T cell therapies. In this issue of Cell, Baker and colleagues developed a large language model (LLM)-assisted scoring framework to streamline this process and as a result identified and validated glycoprotein non-metastatic me...

A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.

Gastrointestinal (GI) cancers represent a significant global health burden, characterized by high incidence, poor prognosis, and limited response to monotherapies. The advent of bispecific antibodies (BsAbs) has introduced a novel therapeutic paradigm, enabling dual targeting of tumor-associated ant...

Clinical Outcomes of Second-Line FOLFIRI Plus Ramucirumab According to Prior Biologic Exposure in Metastatic Colorectal Cancer: A Retrospective Comparison of Prior Bevacizumab and Prior Anti-EGFR Cohorts.

Ramucirumab plus FOLFIRI is an established second-line treatment option for metastatic colorectal cancer (mCRC) after oxaliplatin-based first-line therapy. However, real-world data comparing outcomes according to prior biologic exposure are limited. We retrospectively reviewed patients with mCRC who...

AI-driven discovery of GPNMB CAR T cells as a multi-cancer therapy.

Chimeric antigen receptor (CAR) T cells have demonstrated curative potential in hematologic cancers and increasing efficacy in solid tumors and non-malignant diseases. However, target identification remains a major bottleneck. We developed an artificial intelligence (AI)-driven approach for CAR T ce...

Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review.

Antibody-drug conjugates (ADCs) have transitioned from clinically marginal agents into a defining therapeutic class for solid tumor oncology. In DESTINY-Breast03, trastuzumab deruxtecan achieved a four-fold progression-free survival advantage over trastuzumab emtansine, attributable not to antibody ...

Diagnostic Challenges of Tumor Tissue and Circulating Microsatellite Status Assessment in Metastatic Colorectal Cancer and Their Impact on Access to Immunotherapy: A Real-World Retrospective Study.

Microsatellite instability (MSI) and mismatch repair (MMR) deficiency are key predictive biomarkers for immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC). In real-world practice, however, diagnostic pathways often involve heterogeneous testing modalities, which may lead to d...

The Effect of Anti-Inflammatory Drugs on the Incidence of Colorectal Cancer.

Background/Objectives: Chronic inflammation is a key factor in the development and progression of colorectal cancer (CRC). When COX-2 levels and PGE2 production increase, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA) and selective COX-2 inhibitors, such as celecoxib and rofe...

Synergistic Inhibition of Colorectal Cancer Growth by Combined PI3K and COX-2 Blockade in Cell Lines and Patient-Derived Organoids.

Background/Objectives: PI3K/AKT/mTOR is a key pathway in cell proliferation, metabolism, and survival. Activating PIK3CA mutations are seen in up to 20% of colorectal cancers and are associated with increased cyclo-oxygenase-2 (COX-2) expression. Recent studies demonstrated a significant survival be...

Microsatellite Phenotype as a Guide for Immunotherapy in Colorectal Cancer: Current Status and Future Perspectives.

The therapeutic armamentarium for colorectal cancer (CRC) has been significantly expanded with the introduction of immunotherapy, particularly immune checkpoint inhibitors (ICIs). However, the response to immunotherapy is strongly dependent on microsatellite instability (MSI) status. Tumors with hig...

Tissue-Agnostic Targeting in Solid Tumors: A PRISMA-Compliant Meta-Analysis of Efficacy, Safety, and Resistance Determinants Across Histologies.

Objectives: Tissue-agnostic oncology personalizes treatments based on shared molecular biomarkers, addressing challenges like assay variability, control-arm rigor, and non-proportional hazards. Integrating efficacy, safety, and resistance factors with consistent estimands is essential for evaluating...

Distinct molecular and clinical aggressiveness in very early-onset metastatic colorectal cancer: survival and genomic divergence between patients aged 30-39 versus 40-49 years.

Early-onset colorectal cancer (EOCRC) is increasing worldwide and exhibits clinical heterogeneity. Patients younger than 40 years may constitute a biologically distinct subgroup within EOCRC. We investigated whether 'very early-onset' metastatic colorectal cancer (VEOCRC, ages 30-39) exhibits specif...

Toxicity and Treatment Completion of Neoadjuvant FOLFOXIRI and Chemoradiotherapy in Patients With High-Risk Locally Advanced Rectal Cancer: A Secondary Outcome Analysis of the MEND-IT Trial.

Total neoadjuvant therapy (TNT) is a promising strategy to improve tumor response and oncological outcomes in patients with locally advanced rectal cancer (LARC) , particularly in those with high-risk tumor characteristics. Although triplet chemotherapy (ie, FOLFOXIRI) is currently used exclusively ...

Weight management in obese cancer patients during curative active treatment: protocol for the CANOBESE feasibility study.

Obesity is highly prevalent among patients with cancer and is associated with increased risks of treatment-related complications, poorer oncological outcomes, and long-term morbidity. Despite this, current oncology nutrition guidelines primarily address malnutrition and provide limited direction for...

EMPIRE (NSABP FC-13): a biomarker-driven phase II platform trial evaluating cemiplimab-based immunotherapy in microsatellite-stable colorectal cancer with ctDNA-defined minimal residual disease.

Microsatellite-stable (MSS) colorectal cancer (CRC), which accounts for approximately 85% of cases annually, has demonstrated limited responsiveness to immune checkpoint blockade in the metastatic setting. Circulating tumor DNA (ctDNA) enables sensitive detection of minimal residual disease (MRD) fo...

A novel lactylation-related gene signature deciphers the immunosuppressive microenvironment and stratifies precision therapy in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer mortality, largely due to the heterogeneity of the tumor microenvironment (TME) and the limited efficacy of immunotherapy in microsatellite stable (MSS) tumors. Histone lactylation, a post-translational modification derived from the Warburg e...

[Advances in systemic therapy-driven conversion strategies for locally advanced rectal cancer].

Locally advanced rectal cancer (LARC) remains a major therapeutic challenge in multidisciplinary oncology. The increasing emphasis on early systemic intervention has positioned total neoadjuvant therapy (TNT) as a central treatment paradigm, with the potential to improve control of occult metastatic...

[Progress in the evaluation of tumor response status after neoadjuvant therapy for rectal cancer].

In recent years,neoadjuvant therapy has become an integral part of the standard treatment for locally advanced rectal cancer.However,only approximately 15%-25% of patients achieve pathological complete response(pCR).With advances in tumor immunotherapy,treatment strategies targeting mismatch repair ...

[Analysis of risk factors for long-term severe anastomotic complications following rectal cancer surgery].

Objective: To investigate the risk factors of long-term (>3 months) severe anastomotic complications after rectal cancer surgery. Methods: A case-control study was employed, with the following inclusion criteria for cases: (1) age between 18 and 80 years; (2) history of radical surgery for rectal ca...

TMEM184A-mediated autophagy in MHC-I degradation promotes tumor immune evasion.

The dominance of immunotherapy-insensitive MSS colorectal cancers (CRCs), which represent most cases, contrasts sharply with the treatable MSI-H minority, making this disparity a key obstacle to progress. It is urgent to identify genes driving immune evasion in MSS CRCs. Here, using a genome-wide CR...

Cost-effectiveness of multitarget stool DNA testing for colorectal cancer screening in Chinese primary healthcare settings: a modelling study.

To evaluate the cost-effectiveness of a one-time mt-sDNA-based colorectal cancer screening program compared with no screening, using real-world data from a government-led population-based screening program in Harbin Municipality of China. This modelling study was based on a real-world mt-sDNA CRC sc...

In silico repurposing of clinically approved drugs as potential BRAF inhibitors: a pharmacophore-based virtual screening and experimental investigation.

The BRAFV600E mutation is a key oncogenic driver in multiple cancers. While FDA-approved BRAF inhibitors exist, their efficacy is often limited by drug resistance and adverse effects, necessitating the discovery of novel therapeutic agents. This study aimed to computationally repurpose clinically ap...

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