Consensus, debate, and prospective on pancreatic cancer treatments

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Oct. 10, 2024

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite improvement multi-modality treatment strategies, prognosis pancreatic was not improved dramatically. For resectable or borderline patients, surgical strategy centered on improving R0 resection rate is consensus; however, role neoadjuvant therapy in patients and optimal chemotherapy with without radiotherapy were debated. Postoperative adjuvant gemcitabine/capecitabine mFOLFIRINOX recommended regardless margin status. Chemotherapy as first-line for advanced metastatic included FOLFIRINOX, gemcitabine/nab-paclitaxel, NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan only standard care second-line therapy. Immunotherapy an innovative although anti-PD-1 antibody currently agent approved by MSI-H, dMMR, TMB-high tumors, which represent very small subset cancers. Combination strategies to increase immunogenicity overcome immunosuppressive tumor microenvironment may sensitize immunotherapy. Targeted therapies represented PARP KRAS inhibitors are also under investigation, showing benefits progression-free survival objective response rate. This review discusses current modalities highlights cancer.

Language: Английский

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Treatment Innovations in Pancreatic Cancer: Putting Patient Priorities First

American Society of Clinical Oncology Educational Book, Journal Year: 2025, Volume and Issue: 45(3)

Published: April 2, 2025

Pancreatic adenocarcinoma remains one of the most aggressive and difficult-to-treat solid tumor malignancies, with a high mortality-to-incidence ratio. Globally, pancreatic cancer ranks 12th in terms incidence but sixth for mortality signifying its behavior limited treatment options. While rates many other tumors have substantially improved over past few decades, temporal trends are quite sobering. In United States, from 2000 to 2020, increased, whereas at same time, cancers, such as lung, colorectal, or kidney, fallen appreciably. Is this lack innovation? How do we improve survival patients cancer? chapter, discuss recent advances future directions targeted therapies immunotherapies cancer, provide reasons both optimism caution systemic cancer.

Language: Английский

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Current status of cancer genome medicine for pancreatic ductal adenocarcinoma

Japanese Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis; however, advancements in cancer genome profiling using next-generation sequencing have provided new perspectives. KRAS mutations are the most frequently observed genomic alterations patients with PDAC. However, until recently, it was not considered viable therapeutic target. Although G12C for which targeted therapies already available infrequent PDAC, treatments targeting G12D and pan-KRAS still under development. Similarly, treatment methods KRAS, such as chimeric antigen receptor T-cell therapy, been developed. Several other potential targets identified wild-type For instance, immune checkpoint inhibitors demonstrated efficacy PDAC microsatellite instability-high/deficient mismatch repair tumor mutation burden–high profiles. cases low immunogenicity, combination that enhance effectiveness of being considered. Additionally, homologous recombination deficiencies, including BRCA1/2 mutations, prevalent serve important biomarkers involving poly (adenosine diphosphate-ribose) polymerase platinum-based therapies. Currently, olaparib is maintenance therapy mutation-positive Further developments ongoing genetic abnormalities BRAF V600E fusion genes RET, NTRK, NRG, ALK, FGFR2, ROS1. Overcoming advanced remains formidable challenge; this review outlines latest strategies expected to lead significant advancements.

Language: Английский

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Clinical characterization and therapeutic targeting of fusion genes in oncology

Future Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 24, 2025

Gene fusions represent important oncogenic driver mutations resulting in aberrant cellular signaling. In up to 17% of all solid tumors at least one gene fusion can be identified. Precision therapy targeting signaling has demonstrated effective clinical benefit. Advancements clinically relevant next-generation sequencing and bioinformatic techniques have enabled expansion therapeutic opportunity subpopulations patients with expression. Clinically, tyrosine inhibitors shown efficacy treating expressing cancers. Fusion genes are also clonal mutations, meaning it is a personal cancer target involving cells that patient, not just subpopulation within the mass. Thus, both signal disruption immune directions. This review discusses targeting, resistance, molecular biomarkers.

Language: Английский

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Early-onset enriches the identification of actionable alterations in patients with KRAS wild-type pancreatic ductal adenocarcinoma

ESMO Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 8, P. 100179 - 100179

Published: May 20, 2025

Language: Английский

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Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review

Modern Pathology, Journal Year: 2024, Volume and Issue: 37(9), P. 100554 - 100554

Published: June 29, 2024

Language: Английский

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Advancing Immunotherapy in Pancreatic Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11560 - 11560

Published: Oct. 28, 2024

Pancreatic cancer remains one of the deadliest malignancies, with a consistently low five-year survival rate for past several decades. This is in stark contrast to other cancers, which have seen significant improvement and prognosis due recent developments therapeutic modalities. These modest improvements pancreatic outcomes primarily resulted from minor advances cytotoxic chemotherapeutics, limited progress treatment approaches. A major focus current research further development immunomodulatory therapies characterized by antibody-based approaches, cellular therapies, vaccines. Although initial results utilizing immunotherapy been mixed, clinical trials demonstrated patient outcomes. In this review, we detail these three approaches immunomodulation, highlighting their common targets distinct shortcomings, provide narrative summary completed ongoing that utilize immunomodulation. Within context, aim inform future efforts identifying promising areas warrant exploration.

Language: Английский

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Identifying Actionable Alterations in KRAS Wild-Type Pancreatic Cancer

Targeted Oncology, Journal Year: 2024, Volume and Issue: 19(5), P. 679 - 689

Published: Aug. 10, 2024

Language: Английский

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Redefining pancreatic cancer management with tumor-agnostic precision medicine

Carcinogenesis, Journal Year: 2024, Volume and Issue: 45(11), P. 836 - 844

Published: Nov. 1, 2024

Abstract Precision oncology and tumor-agnostic drug development provide hope for enhancing outcomes among patients with pancreatic cancer. Tumor-agnostic therapies have emerged across various tumor types, driven by insights into shared biomarkers. In the case of cancer, prevalence KRAS gene mutation is noteworthy. However, there exist other actionable alterations, such as BRCA1/2 mutations fusion genes (BRAF, FGFR2, RET, NTRK, NRG1, ALK), which present potential targets therapy. Notably, drugs demonstrated efficacy in specific subsets cancer who harbor these genetic alterations. Despite rarity NTRK fusions larotrectinib entrectinib exhibited effectiveness fusion-positive cancers. Additionally, repotrectinib, a next-generation inhibitor, has shown promising activity positive developed acquired resistance to previous inhibitors. Immune checkpoint inhibitors, pembrolizumab dostarlimab, proven be effective dMMR/MSI-H Moreover, targeted BRAF V600, RET fusions, HER2/neu overexpression displayed results patients. Emerging like NRG FGFR2 TP53 mutations, G12C avenues revolutionize treatment focusing on It crucial continue implementing comprehensive screening strategies that encompass ability detect all This will essential identifying may benefit from therapies.

Language: Английский

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Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: KRAS and beyond

Expert Review of Molecular Diagnostics, Journal Year: 2024, Volume and Issue: 24(5), P. 355 - 362

Published: May 3, 2024

Introduction A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.

Language: Английский

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