Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 389(23), P. 2125 - 2139

Published: Oct. 22, 2023

G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. Monotherapy KRAS inhibitors has yielded only modest efficacy. Combining the inhibitor sotorasib panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be effective strategy.

Language: Английский

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Colorectal cancer

The Lancet, Journal Year: 2024, Volume and Issue: 404(10449), P. 294 - 310

Published: June 20, 2024

Language: Английский

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Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 66, P. 102315 - 102315

Published: Nov. 14, 2023

Language: Английский

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Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(6), P. 982 - 993

Published: April 8, 2024

Adagrasib, an irreversible, selective KRASG12C inhibitor, may be effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients previously treated unresectable or metastatic cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four With a median follow-up 11.9 months, ORR 34.0%, disease control 85.1%, and duration 5.8 months (95% confidence interval [CI], 4.2-7.6). Median progression-free survival 6.9 CI, 5.7-7.4) overall 15.9 11.8-18.8). Treatment-related adverse events (TRAEs) occurred all patients; grade 3-4 27.7% no 5. No TRAEs led to discontinuation. Exploratory analyses suggest circulating tumor DNA identify features acquired resistance.

Language: Английский

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Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 245 - 245

Published: Jan. 28, 2024

Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay treatment for metastatic chemotherapy, but unfortunately, even with recent progress, overall survival still poor. Colorectal heterogeneous disease, underlying genetic differences among tumors can define behavior prognosis disease. Given limitations cytotoxic research has focused on developing targeted therapy based molecular subtyping. Since early 2000s, multiple therapies have demonstrated efficacy in treating received FDA approval. epidermal growth factor receptor (EGFR), vascular endothelial (VEGF), DNA mismatch repair pathways promising results therapies. As new gene mutations proteins involved oncogenesis are identified, targets will continue to emerge. We herein provide summary updated literature regarding patients mCRC.

Language: Английский

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Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(24), P. 2918 - 2927

Published: June 4, 2024

Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination pembrolizumab improves outcomes compared standard of care (SOC) mismatch repair proficient or not microsatellite instability high (pMMR MSI-H) mCRC.

Language: Английский

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Colorectal cancer: Recent advances in management and treatment

World Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 15(9), P. 1136 - 1156

Published: Aug. 29, 2024

Colorectal cancer (CRC) is the third most common worldwide, and second cause of cancer-related death. In 2020, estimated number deaths due to CRC was approximately 930000, accounting for 10% all worldwide. Accordingly, there a vast amount ongoing research aiming find new improved treatment modalities that can potentially increase survival decrease overall morbidity mortality. Current management strategies include surgical procedures resectable cases, radiotherapy, chemotherapy, immunotherapy, in addition their combination, non-resectable tumors. Despite these options, remains incurable 50% cases. Nonetheless, significant improvements techniques have allowed approaches be frequently updated, leading availability drugs therapeutic strategies. This review summarizes recent CRC, with special emphasis on are currently being studied great potential improve prognosis lifespan patients CRC.

Language: Английский

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Multi-stage mechanisms of tumor metastasis and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 11, 2024

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.

Language: Английский

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Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e009415 - e009415

Published: Jan. 1, 2025

Background Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes the third-line and subsequent treatments of patients microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance antitumor effect immunotherapy. However, RT exposure on receiving ICIs targeted therapy remains unclear. This study aimed to investigate association between clinical responses fruquintinib (a highly selective tyrosine kinase inhibitor vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) previously treated MSS-mCRC explore predictive biomarkers. Methods In this prospective observational study, mCRC F&S as or treatment were enrolled. Eligible divided into cohort (RTC) non-RT (NRTC) according their history. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control (DCR), progression-free survival (PFS), overall (OS), safety. Pretreatment fecal serum samples collected for microbiome analysis, metabolome immune signatures identify biomarkers treatment. Results A total 55 included, which 25 RTC 30 NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% 36.7%, p=0.002), median PFS (6.2 2.7 months, p<0.001), OS (14.8 5.9 p=0.019) noted than those enrichment Lactobacillus , Bifidobacterium PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) significantly predicted better PFS, whereas guanosine interleukin-10 predominated NRTC negatively correlated OS. Conclusions Patients benefited from MSS-mCRC. Gut microbiota, metabolites, cytokines help predict mCRC, be helpful decision-making. Trial registration number ClinicalTrials.gov identifier: NCT05635149 .

Language: Английский

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Digestive cancers: mechanisms, therapeutics and management

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 14, 2025

Abstract Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% annual cases cancer deaths. The etiologies, molecular features, therapeutic management these entities highly heterogeneous complex. Over last decade, genomic functional studies have provided unprecedented insights into biology cancers, identifying genetic drivers tumor progression key interaction points cells with immune system. This knowledge is continuously translated novel treatment concepts targets, which dynamically reshaping landscape tumors. In this review, we provide a concise overview etiology pathology six most common cancers system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, colorectal cancers. We comprehensively describe current stage-dependent pharmacological malignancies, chemo-, targeted, immunotherapy. For each entity, an recent advancements research progress. Finally, how heterogeneity evasion deepen our understanding therapy resistance outlook on innovative strategies that will shape future CAR-T cell therapy, antibody-drug conjugates targeted therapies.

Language: Английский

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