Exploiting Non-Oncogene Addiction for Overcoming Drug Resistance in Metastatic Tumors

The field of cancer therapeutics has seen significant advancements with the development and FDA approval of drugs targeting oncogenes, such as immune checkpoint inhibitors and tyrosine kinase inhibitors. Despite these advancements, challenges like metastatic spread, cancer repopulation, and acquired cancer cell resistance (M-CRAC) persist, particularly in relapsed or refractory tumor diseases. These challenges hinder the achievement of complete remission (CR) or continuous complete remission (cCR). Addressing these issues necessitates a focus on non-oncogene addiction, where genes aberrantly expressed due to oncogenic mutations play a crucial role in maintaining tumor integrity and survival. These genes, although not directly druggable, are interconnected within tumor-specific networks. Recent studies suggest that targeting these non-oncogene addictions, whether primary or therapeutically induced, could offer new avenues for treating metastatic tumors lacking driver mutations and neoplasias in advanced stages. However, the therapeutic exploitation of non-oncogene addiction remains underexplored, highlighting a gap in current research that needs to be addressed.

This research topic aims to explore the therapeutic potential of exploiting primary or therapeutically established non-oncogene addiction. The main objectives include understanding the role of non-oncogene addiction in tumor survival and stress responses, investigating synthetic lethality as a strategy to overcome drug resistance, and assessing the differential activity of drug combinations at various metastatic sites. Additionally, the research seeks to identify therapeutic windows that allow for the induction of non-oncogene addiction with minimal toxicity, ultimately aiming to attenuate or resolve M-CRAC in relapsed or refractory tumor diseases.

To gather further insights in the therapeutic exploitation of non-oncogene addiction, we welcome articles addressing, but not limited to, the following themes:

• Studies on diagnostics of oncogene addiction and the interaction of oncogenic events with non-oncogene addiction across different tumor types.
• Combination therapies targeting non-oncogene addiction.
• In vitro studies or clinical trials focused on therapeutically establishing non-oncogene addiction in tumors without driver mutations.
• The induction of non-oncogene addiction in relapsed or refractory neoplasias.
• Exploration of therapeutic windows to facilitate non-oncogene addiction and synthetic lethality with reduced toxicity.

Keywords: Non-oncogene, addiction, stress sensitivity of tumors, tumor tissue editing

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.