The CXCL1-CXCR2 Axis as a Component of Therapy Resistance, a Source of Side Effects in Cancer Treatment, and a Therapeutic Target.

IF 4.5 2区医学 Q1 ONCOLOGY

Cancers Pub Date : 2025-05-15 DOI:10.3390/cancers17101674

Jan Korbecki, Mateusz Bosiacki, Maciej Pilarczyk, Marcin Kot, Piotr Defort, Ireneusz Walaszek, Dariusz Chlubek, Irena Baranowska-Bosiacka

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引用次数: 0

Abstract

CXCL1 (Gro-α, MGSA) is a chemokine functionally similar to CXCL8/IL-8, as both activate the same receptor, CXCR2. CXCL1 levels are frequently elevated in tumors compared to healthy tissue, where they play a key role in promoting cancer cell migration, angiogenesis, and neutrophil recruitment. While the involvement of CXCL1 in tumor progression is well established, its relevance to cancer therapy remains underexplored. This review examines the therapeutic potential of targeting CXCL1 and its receptor, CXCR2, in cancer treatment. It discusses anti-CXCL1 antibodies and CXCR2 antagonists, including AZD5069, SB225002, SCH-479833, navarixin/SCH-527123, ladarixin/DF2156A, and reparixin, as well as strategies to enhance CXCR2 expression in lymphocytes during adoptive cell therapy to improve immunotherapy outcomes. Particular attention is given to the role of CXCL1 in treatment resistance, including resistance to chemotherapy, radiotherapy, and anti-angiogenic therapy. Cancer therapies often upregulate CXCL1 expression, which in turn drives treatment resistance. Additionally, this review explores the contribution of CXCL1 to therapy-induced side effects, such as chemotherapy-induced metastasis, neuropathy, nephrotoxicity, diarrhea, and cardiotoxicity. CXCR2 inhibitors are well tolerated by patients in clinical trials. However, the limited number of studies evaluating these agents in combination with standard chemotherapy precludes any definitive conclusions.

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CXCL1-CXCR2轴作为治疗耐药的组成部分，癌症治疗中的副作用来源和治疗靶点。

CXCL1 （Gro-α， MGSA）是一种功能类似于CXCL8/IL-8的趋化因子，因为它们激活相同的受体CXCR2。与健康组织相比，CXCL1水平在肿瘤中经常升高，在肿瘤中它们在促进癌细胞迁移、血管生成和中性粒细胞募集中起关键作用。虽然CXCL1参与肿瘤进展已被证实，但其与癌症治疗的相关性仍未得到充分探讨。本文综述了靶向CXCL1及其受体CXCR2在癌症治疗中的治疗潜力。本文讨论了抗cxcl1抗体和CXCR2拮抗剂，包括AZD5069、SB225002、sch479833、navarixin/ sch527123、ladarixin/DF2156A和reparixin，以及在过继细胞治疗期间提高CXCR2在淋巴细胞中的表达以改善免疫治疗效果的策略。特别关注CXCL1在治疗耐药中的作用，包括对化疗、放疗和抗血管生成治疗的耐药。癌症治疗通常会上调CXCL1的表达，从而导致治疗耐药性。此外，本综述探讨了CXCL1在治疗性副作用中的作用，如化疗诱导的转移、神经病变、肾毒性、腹泻和心脏毒性。在临床试验中，患者对CXCR2抑制剂耐受良好。然而，评估这些药物与标准化疗联合使用的研究数量有限，因此无法得出任何明确的结论。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancers Medicine-Oncology

CiteScore

8.00

自引率

9.60%

发文量

5371

审稿时长

18.07 days

期刊介绍： Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.