12/27/2023 0 Comments Keynote 048![]() Mucoepidermoid carcinoma (MEC) accounts for 10% of SGTs and has a poor prognosis. Salivary gland tumors (SGTs) are heterogeneous tumors that range from benign masses to aggressive high-grade carcinomas with distant metastatic potential and limited response to chemotherapy. In addition, these agents could also be tested to assess their efficacy in combination with immunotherapy in recurrent and metastatic settings or in combination with radiotherapy and immunotherapy in curative settings. Here, we will discuss the possibility of using these compounds as radiosensitisers, which could be assessed as safe and effective alternatives to chemotherapy, particularly for patients with HNSCC that are not suitable for concurrent chemotherapy due to their age or co-morbidities or in metastatic settings. Recently, imidazole-based or quinone-based anti-malarial compounds have drawn considerable attention as potential radiosensitisers in several cancers. However, there is new hope that a treatment strategy that incorporates agents that act as radiosensitisers to improve the efficacy of conventional radiotherapy could be an alternative to more toxic chemotherapeutic agents. Currently, there are several promising anti-cancer drugs available, but there has been very limited success so far in replacing concurrent chemoradiation due to their low efficacy or increased toxicities. Thus, there is an urgent need to assess other less toxic treatment modalities, which could become an alternative to chemoradiation in HNSCC. These patients are often treated with radiotherapy alone resulting in poor locoregional control and worse survival outcomes. In addition, patients with significant co-morbidities, or older patients, cannot tolerate or do not benefit from concurrent chemoradiation. The addition of platinum chemotherapy to primary radiotherapy (chemoradiation) improves survival outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but it carries a high incidence of acute and long-term treatment-related complications, resulting in a poor quality of life. Nivolumab has also been shown to improve OS for recurrent or metastatic HNSCC after previous platinum-based chemotherapy was compared to the investigators' choice of second-line treatments (docetaxel, methotrexate or cetuximab ), resulting in nivolumab's approval as a second-line treatment after platinum-based chemotherapy. Moreover, pembrolizumab plus chemotherapy significantly improved OS in the total population, with safety comparable to the EXTREME regimen as a first-line treatment, resulting in the approval of pembrolizumab for recurrent or metastatic HNSCC as a first-line treatment as well. to cetuximab with platinum chemotherapy plus 5-FU (EXTREME regimen)-showed that pembrolizumab monotherapy significantly improved overall survival (OS) over the EXTREME regimen in the PD-L1 combined pathology score (CPS) ≥20 and ≥1 populations. The KEYNOTE-048 study-a randomised phase 3 trial comparing pembrolizumab as a monotherapy or in combination with platinum chemotherapy plus 5-FU vs. We will discuss how PDAC tumor cells bypass IFN-I signaling pathways and explore how these pathways can be co-opted or re-engaged to enhance the therapeutic outcome. This review will focus on the pivotal role played by IFN-I in promoting tumor cell–immune cell cross talk in PDAC. Understanding where defects in innate immune triggers render the PDAC tumor–immune interface less effective, or how T-cell function is suppressed will help develop more effective treatments and harness the immune system for durable outcomes. While PDAC exhibits intrinsic features that have the potential to engage immune cells, particularly following chemotherapy, these immune-sensing mechanisms are ineffective. Damage- or stress-mediated activation of nucleic acid-sensing pathways triggers type I interferon (IFN-I) responses that activate innate immune cells and natural killer cells, promote maturation of dendritic cells, and stimulate adaptive immunity. ![]() Cytotoxic or metabolic stress produced by radiation and/or chemotherapy can act as potent immune triggers and prime immune responses. ![]() Alterations in tumor DNA such as genomic instability, high tumor mutation burden, and/or defects in DNA damage repair are associated with responses to both immunotherapy and chemotherapy. Intrinsic tumor cell properties govern interactions with the immune system. These features classify PDAC as immunologically “cold.” However, the presence of tumor T cells is a favorable prognostic feature in PDAC. PDAC tumors often have low infiltration of tumor CD8 ⁺ T cells and a highly immunosuppressive microenvironment. ![]() However, pancreatic ductal adenocarcinomas (PDACs) exhibit poor responses to immune checkpoint inhibitors with immunotherapy-based trials not generating convincing clinical activity. Immunotherapy has revolutionized the treatment of many cancer types.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |