Antitumor therapies have conventionally been evaluated based on their capacity to eliminate malignant cells. However, growing evidence highlights that drugs targeting specific oncogenic pathways may induce off-target effects able to interfere with the broader tumor microenvironment (TME). These critical interactions can reshape immune cell dynamics, disrupt metabolic pathways, alter extracellular matrix, and modify stromal architecture, ultimately affecting therapeutic efficacy and resistance.

The interplay between cancer therapies and the immune system is now recognized as a key determinant of treatment success. Chemotherapy is significantly more effective in immunocompetent than immunodeficient hosts, highlighting the crucial role of immune surveillance in influencing patient outcomes. Beyond direct cytotoxicity, anticancer drugs also work as immunomodulators, inducing metabolic reprogramming, modifying key signaling cascades, and remodeling the TME, either enhancing or impairing long-term therapeutic responses. These changes influence not only tumor regression but also mechanisms of resistance and disease progression.

This Research Topic aims to explore the multifaceted effects of anticancer therapies, ranging from immune modulation, metabolic shifts and post-translational modifications to alterations in signaling networks and stromal interactions. By combining cutting-edge research and innovative perspectives, we pursue to extend our understanding of how therapies reshape the TME and how these insights can propose new strategies to enhance therapeutic efficacy, overcome resistance, and improve patient outcomes.

To provide a comprehensive perspective on this complex cross-talk, we welcome contributions across various article types, including Original Research, Brief Research Reports, Methods, Reviews, and Mini-Reviews.

We encourage submissions on, but not limited to, the following themes:

• Cancer therapies impacting immune response

• Interplayers in cancer suppression

• Rewiring metabolism and TME dynamics

• Alteration/deregulation of proteins and enzymes in the TME after anticancer treatments

• Innovative perspectives and therapeutic strategies

Are you interested in contributing a manuscript to this Research Topic?

Beyond Tumor Cell Killing: Unraveling the Multifaceted Impact of Antitumor Therapies on the Tumor Microenvironment