Clinical Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 17(3), P. 451 - 456
Published: Feb. 23, 2024
Language: Английский
Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(12), P. 843 - 863
Published: Oct. 16, 2023
Language: Английский
Citations
61
CA A Cancer Journal for Clinicians, Journal Year: 2024, Volume and Issue: 74(5), P. 433 - 452
Published: May 30, 2024
Tumor-agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero specific genetic anomalies responsible for fueling malignant growth. The watershed moment tumor-agnostic arrived 2017, with US Food and Drug Administration's historic approval pembrolizumab, an immune checkpoint inhibitor. This milestone marked marriage genomics immunology fields, as immunotherapeutic agent gained genomic biomarkers, specifically, microsatellite instability-high mismatch repair deficiency (dMMR). Subsequently, NTRK inhibitors, designed to combat gene fusions prevalent various tumor types, including pediatric cancers adult solid tumors, further underscored potential therapies. Administration approvals targeted (BRAF V600E, RET fusion), immunotherapies (tumor mutational burden ≥10 mutations per megabase, dMMR) antibody-drug conjugate (Her2-positive-immunohistochemistry 3+ expression) pan-cancer efficacy have continued, offering newfound hope patients grappling advanced that harbor particular biomarkers. In this comprehensive review, authors delve into expansive landscape tissue-agnostic targets drugs, shedding light rationale underpinning approach, hurdles it faces, presently approved therapies, voices from patient advocacy perspective, tantalizing prospects horizon. is welcome advance transcends boundaries histology location provide personalized options.
Language: Английский
Citations
22
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Aug. 9, 2024
The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.
Language: Английский
Citations
20
ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(4), P. 967 - 990
Published: March 19, 2024
Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized effective disease management. Identification key driver mutations molecular profiling have deepened our comprehension genetic alterations in cancer, facilitating targeted therapy immunotherapy selection. Biomarkers such as microsatellite instability (MSI) DNA mismatch repair deficiency (dMMR) guide decisions, opening avenues for immunotherapy. Emerging liquid biopsies, artificial intelligence, machine learning promise to revolutionize early detection, monitoring, selection precision medicine. Despite these advancements, ethical regulatory challenges, including equitable access data privacy, emphasize importance responsible implementation. The dynamic nature with its tumor heterogeneity clonal evolution, underscores necessity adaptive strategies. future lies potential enhance patient care, clinical outcomes, understanding this intricate disease, marked by ongoing evolution field. current reviews focus on providing in-depth knowledge various diverse approaches utilized against at both biochemical levels.
Language: Английский
Citations
17
Immunology, Journal Year: 2024, Volume and Issue: 173(2), P. 209 - 226
Published: March 22, 2024
Abstract Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% these tumours are proficient mismatch repair (pMMR)‐microsatellite instability‐low (MSI‐L)/microsatellite stable (MSS) CRC known as ‘cold’ that resistant to immunosuppressive drugs. Monotherapy programmed death 1 (PD‐1)/programmed ligand (PD‐L1) inhibitors ineffective for treating MSS CRC, making immunotherapy bottleneck. Recent studies have found the multi‐pathway regimens combined PD‐1/PD‐L1 can enhance efficacy anti‐PD‐1/PD‐L1 in by increasing number CD8+ T cells, upregulating PD‐L1 expression improving tumour microenvironment. This paper reviews research progress combination cytotoxic T‐lymphocyte–associated antigen 4 (CTLA‐4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy epigenetic drugs treatment pMMR‐MSI‐L/MSS CRC.
Language: Английский
Citations
15
Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(1), P. e008079 - e008079
Published: Jan. 1, 2024
Background Microsatellite stable colorectal liver metastases (MSS CLM) maintain an immunosuppressive tumor microenvironment (TME). Historically, immune-based approaches have been ineffective. VB-111 (ofranergene obadenovec) is a genetically-modified adenoviral vector targeting the TME; its unique dual mechanism induces immune response and disrupts neovascularization. Checkpoint inhibition may synergize induced by viral-mediated anti-angiogenic gene therapy. We aimed to examine safety antitumor activity of nivolumab in patients with refractory MSS CLM characterize immunological treatment-response. Methods This was phase II study adult histologically-confirmed who progressed on prior A priming dose 1×10 13 viral particles given intravenously 2 weeks starting biweekly 240 mg continued every 6 weeks. The combination until disease progression or unacceptable toxicity. primary objectives were overall rate safety/tolerability. Secondary included median survival progression-free survival. Correlative studies performed paired biopsies blood. Results Between August 2020 December 2021, 14 enrolled age 50.5 years (40–75), 14% women. Median follow-up 5.5 months. Of 10 evaluable patients, failed demonstrate radiographic responses; at best, had disease. months (95% CI: 2.3 10.8), 1.8 1.4 1.9). most common grade 3–4 treatment-related adverse events fever/chills, influenza-like symptoms, lymphopenia. No deaths reported. Qualitative analysis immunohistochemical staining did not significant infiltration after treatment, except for one patient exceptional (26.0 months). Immune peripheral blood mononuclear cells showed increase PD-1 high Ki67 CD8 + T HLA-DR dose. Plasma cytokines interleukin-10 necrosis factor-α increased treatment both drugs. Conclusion In CLM, improve but tolerated minimal toxicities. While challenging distinguish between antiviral antitumor, correlative demonstrated activation proliferation systemically that poorly sustained. Trial registration number NCT04166383 .
Language: Английский
Citations
9
Cancers, Journal Year: 2023, Volume and Issue: 15(17), P. 4245 - 4245
Published: Aug. 24, 2023
Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients the metastatic setting 15% early-stage disease. Following impressive clinical activity inhibitors setting, deep long-lasting responses, development has expanded Several phase II trials have demonstrated rate pathological complete some even spared from surgery. However, both settings, not all respond short, emphasizing importance ongoing search for accurate biomarkers. While various biomarkers response been evaluated context CRC, including B2M JAK1/2 mutations, TMB, WNT pathway Lynch syndrome, mixed results, liver metastases lack such strategies. To improve patient selection treatment outcomes, further research required identify additional refine existing ones. This will allow personalized approaches integration novel therapeutic strategies CRC metastases.
Language: Английский
Citations
22
Annals of Coloproctology, Journal Year: 2024, Volume and Issue: 40(2), P. 89 - 113
Published: April 30, 2024
Colorectal cancer is the third most common in Korea and leading cause of death from cancer. Treatment outcomes for colon are steadily improving due to national health screening programs with advances diagnostic methods, surgical techniques, therapeutic agents.. The Colon Cancer Multidisciplinary (KCCM) Committee intends provide professionals who treat up-to-date, evidence-based practice guidelines improve help them make decisions that reflect their patients' values preferences. These have been established by consensus reached KCCM Guideline based on a systematic literature review evidence synthesis considering insurance system real clinical settings. Each recommendation presented strength level committee.
Language: Английский
Citations
6
Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2796 - 2796
Published: Aug. 8, 2024
Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors have significantly improved patient outcomes, their effectiveness is mostly limited to tumors with microsatellite instability (MSI-H/dMMR) or an increased tumor mutational burden, which comprise 10% cases. Advancing personalized medicine in CRC hinges on identifying predictive biomarkers guide treatment decisions. This comprehensive review examines established tissue markers such as KRAS and HER2, highlighting roles resistance anti-EGFR agents discussing advances targeted therapies for these markers. Additionally, this summarizes encouraging data promising therapeutic targets highlights clinical utility liquid biopsies. By synthesizing current evidence knowledge gaps, provides clinicians researchers a contemporary understanding biomarker landscape CRC. Finally, future directions challenges translating into practice, goal enhancing approaches colorectal patients.
Language: Английский
Citations
5
Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Aug. 26, 2024
Abstract Colorectal cancer (CRC) ranks as the third most prevalent globally. It’s recognized that molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines current classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like (LLS), sporadic cases. Despite advances understanding these genetic backgrounds, clinical trials have not conclusively differentiated efficacy immune checkpoint inhibitors among subgroups. Therefore, while this details characteristics their general implications for prognosis, it also highlights limitations need more refined studies to ascertain tailored therapeutic strategies each subtype. Furthermore, summarizes completed ongoing studies, emphasizing importance developing treatments aligned closely with profiles. By discussing aspects, seeks provide comprehensive analysis oncological characteristics, presenting detailed prognosis CRC.
Language: Английский
Citations
5