免疫疗法彻底改变了癌症管理,基于抗体的治疗由于其优越的药效学而领先,包括增强的有效性和特异性。然而,这些疗法受到诸如延长半衰期等限制的阻碍,组织和肿瘤渗透不良,和最小的口服生物利用度。此外,它们的免疫原性会引起不良影响。因此,焦点转向基于小分子的免疫疗法,它有可能克服这些缺点。作为一个有希望的替代方案,小分子提供治疗抗体和免疫调节剂的好处,组合时通常会产生协同效应。小分子癌症免疫疗法的最新进展值得注意,以抑制剂为特征,激动剂,和降解物作为免疫调节剂。本文深入探讨了小分子免疫治疗在癌症治疗中的现状,突出了靶向关键途径如Toll样受体(TLR)的新型药物,PD-1/PD-L1,趋化因子受体,和干扰素基因(STING)的刺激物。这篇综述强调了新发现的分子实体及其在肿瘤发生中的调节作用。其中许多已经进入临床试验,旨在提供癌症治疗前沿发展的全面快照,由小分子免疫调节剂驱动。
Immunotherapy has revolutionized cancer management, with antibody-based treatments leading the charge due to their superior pharmacodynamics, including enhanced effectiveness and specificity. However, these therapies are hampered by limitations such as prolonged half-lives, poor tissue and tumor penetration, and minimal oral bioavailability. Additionally, their immunogenic nature can cause adverse effects. Consequently, the focus is shifting towards small-molecule-based immunotherapies, which potentially overcome these drawbacks. Emerging as a promising alternative, small molecules offer the benefits of therapeutic antibodies and
immunomodulators, often yielding synergistic effects when combined. Recent advancements in small-molecule cancer immunotherapy are notable, featuring inhibitors, agonists, and degraders that act as
immunomodulators. This article delves into the current landscape of small-molecule immunotherapy in cancer treatment, highlighting novel agents targeting key pathways such as Toll-like receptors (TLR), PD-1/PD-L1, chemokine receptors, and stimulators of interferon genes (STING). The review emphasizes newly discovered molecular entities and their modulatory roles in tumorigenesis, many of which have progressed to clinical trials, that aims to provide a comprehensive snapshot of the evolving frontier in cancer treatment, driven by small-molecule
immunomodulators.