Research Topic

Targeting the ErbB/Her receptor family for cancer therapy: connecting oncogenes with immunity

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The ErbB/Her oncogene family has proven to be relevant to human cancer, in particular, anti-Her1/EGFR and anti-Her2/neu targeted therapies are currently used in oncology medical practice, including both small tyrosine kinase inhibitors (STKI) and therapeutic monoclonal antibodies. The discovery of the ...

The ErbB/Her oncogene family has proven to be relevant to human cancer, in particular, anti-Her1/EGFR and anti-Her2/neu targeted therapies are currently used in oncology medical practice, including both small tyrosine kinase inhibitors (STKI) and therapeutic monoclonal antibodies. The discovery of the ErbB/Her gene family allowed for the establishment of the connection between oncogenes and receptor tyrosine kinases (RTK). ErbB/Her-targeting therapies have supported the oncogene addiction hypothesis. Inhibition of RTK signaling pathways induces cell growth arrest and tumor cell death. Uncovering the innate and acquired resistance mechanisms to these targeted therapies is a major scientific challenge to optimizing their clinical application, a corresponding issue that has been addressed in previous Frontiers Research Topics.

Experimental and clinical evidence accumulated over time suggests a connection between RTK oncogenes and immunity. ErbB/Her oncogene family activation promotes tumor immune escape by downregulation of tumor immunogenicity (class I MHC expression and antigen processing machinery) and tumor-induced immunosuppression (Fas-L, PD-L1, immunosuppressive cytokines, etc.). Moreover, the ErbB/Her oncogene family activation also promotes tumor progression by the phenomenon of cancer-related inflammation (oncogene-driven tumor intrinsic inflammation).

Therapies targeting the ErbB/Her receptor family could modulate the crosstalk between tumor cells and the immune system; therefore, the combination of therapy with immune modulators and anti-inflammatory drugs is being actively investigated. Additionally, experimental and clinical evidence of antitumor immunity enhancement induced by anti-Her1 and anti-Her2 antibodies is being gathered. Two different mechanisms have been postulated to explain this immunomodulatory effect. Firstly, the tumor antigen cross-presentation induced by the interaction between antibody-activated NK cells and DC; and secondly, the immunogenic cell death induced by anti-erbB/Her antibodies. ErbB/Her receptor family-targeting Ab-based therapy has the potential to reverse the immunosuppressive tumor microenvironment and to stop tumor progression. Understanding such tumor-associated biological phenomena might contribute to transforming advanced cancer into a long-term controllable chronic disease.

Potential contributors to this Research Topic are encouraged to discuss the following issues related to ErbB/Her-targeting therapy:

1) The impact of its immunomodulatory effect in patient survival.
2) The optimization of the treatment schedule for enhancing antitumor immunity.
3) The predictive value of natural anti-Erb/Her specific T-cell response.
4) The differential approaches for STKI and monoclonal antibodies aiming to enhance antitumor immunity.
5) The adaptive resistance mechanisms to induced antitumor immunity.
6) The combination therapy able to maximize anti-tumor immunity.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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