Targeting cytokine and chemokine signaling pathways for cancer therapy

Cytokines are critical in regulating immune responses and cellular behavior,playing dual roles in both normal physiology and the pathology of diseases such as cancer.These molecules,including interleukins,interferons,tumor necrosis factors,chemokines,and growth factors like TGF-β,VEGF,and EGF,can promote or inhibit tumor growth,influence the tumor microenvironment,and impact the efficacy of cancer treatments.Recent advances in targeting these pathways have shown promising therapeutic potential,offering new strategies to modulate the immune system,inhibit tumor progression,and overcome resistance to conventional therapies.In this review,we summarized the current understanding and therapeutic implications of targeting cytokine and chemokine signaling pathways in cancer.By exploring the roles of these molecules in tumor biology and the immune response,we highlighted the development of novel therapeutic agents aimed at modulating these pathways to combat cancer.The review elaborated on the dual nature of cytokines as both promoters and suppressors of tumorigenesis,depending on the context,and discussed the challenges and opportunities this presents for therapeutic intervention.We also examined the latest advancements in targeted therapies,including monoclonal antibodies,bispecific antibodies,receptor inhibitors,fusion proteins,engineered cytokine variants,and their impact on tumor growth,metastasis,and the tumor microenvironment.Additionally,we evaluated the potential of combining these targeted therapies with other treatment modalities to overcome resistance and improve patient outcomes.Besides,we also focused on the ongoing research and clinical trials that are pivotal in advancing our understanding and application of cytokine-and chemokine-targeted therapies for cancer patients.

Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors

Immunotherapy,particularly with immune checkpoint inhibitors,has significantly transformed cancer treatment.Despite its success,many patients struggle to respond adequately or sustain long-lasting clinical improvement.A growing consensus has emerged that radiotherapy(RT)enhances the response rate and overall efficacy of immunotherapy.Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results,establishing itself as a dynamic and thriving area of research,clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results,suggesting the need for a more nuanced understanding.This review provides a balanced and updated analysis of the combination of immunotherapy and RT.We summarized the preclinical mechanisms through which RT boosts antitumor immune responses andmainly focused on the outcomes of recently updated clinical trials,including those that may not have met expectations.We investigated the optimization of the therapeutic potential of this combined strategy,including key challenges,such as fractionation and scheduling,lymph node irradiation,and toxicity.Finally,we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy,providing a realistic perspective on the current state of research and potential future directions.