免疫疗法彻底改变了癌症治疗，基于抗体的治疗因其卓越的药效（包括增强的有效性和特异性）而处于领先地位。然而，这些疗法受到半衰期延长、组织和肿瘤渗透性差以及口服生物利用度极低等限制的阻碍。此外，它们的免疫原性可能会引起不利影响。因此，焦点转向基于小分子的免疫疗法，这有可能克服这些缺点。小分子作为一种有前途的替代品而出现，具有治疗性抗体和免疫调节剂的优点，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引人注目，其中包括充当免疫调节剂的抑制剂、激动剂和降解剂。本文深入探讨了小分子免疫疗法在癌症治疗中的现状，重点介绍了针对关键通路的新型药物，例如 Toll 样受体 (TLR)、PD-1/PD-L1、趋化因子受体和干扰素基因刺激剂 (STING) ）。该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，其中许多已进入临床试验，旨在提供由小分子免疫调节剂驱动的癌症治疗不断发展的前沿的全面概况。版权所有 © 2024。已发布爱思唯尔 B.V.

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.Copyright © 2024. Published by Elsevier B.V.