Why TKI Therapy Targeting Minority Population of Tumor Cells Could Achieve Complete Control of Entire Tumor: The Self-Driven and Non-Autonomous Replication in Cancer and Their Connection through Inflammation

Abstract

Kangla Tusung, Xu Zhang, Hui Zhang and Jinming Zhao

Despite wide application of targeted therapy with small molecule tyrosine kinase inhibitors (TKI) in cancer clinic, some questions for the mechanisms of these inhibitors remain unresolved. For example, how can a tumor be completely controlled for extended period (more than a year) by the drug when the target population in the tumor is not even in majority? Here we report our observations in one such case of lung cancer and provide explanation for this long-awaited clinical puzzle. Our analyses indicate that in many of the similar cases, the cancer is composed of two populations of tumor cells, one capable of autonomous (or self-driven) replication through the known mutation, and the replication of the other is inflammationdependent. The connection is through inflammation induced by the tumor cells capable of self-driven replication. The control of this population by TKI terminates induction of inflammation thus results in control of the non-autonomous population. The identification of these two replicating tumor cells and their relationship holds many answers to current clinical confusions in many cancer cases where accelerated tumor progression, high inflammation and loss of therapy efficacy are often the common feature. By understanding these processes, we can begin to manage cancer in a more proactive manner to avoid the once recognized unavoidable fate of cancer

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