Attacking c-Myc: _targeted and Combined Therapies for Cancer

Title:Attacking c-Myc: _targeted and Combined Therapies for Cancer

Volume: 20 Issue: 42

Author(s): Huilin Huang, Hengyou Weng, Hui Zhou and Lianghu Qu

Affiliation:

Keywords: c-Myc, _targeted cancer therapy, combined therapy, MicroRNA, natural agent.

Abstract: The onset of cancer is a complex process that is driven by the accumulation of multiple genetic mutations. However, the fact that inhibition of a single oncogene can impair the proliferation and survival of cancer cells due to their “oncogene addiction” provides implications for the so-called “molecular _targeted therapy” in cancer treatment. The oncogenic transcription factor c-Myc is overexpressed in many types of cancers, and as a typical oncogene to which many cancers are addicted, c-Myc is necessary for the rapid proliferation of cancer cells. Strategies aimed at _targeting c-Myc, including interfering with c-Myc synthesis, stability and transcriptional activity, have emerged as effective cancer treatments. We have recently shown that a natural agent, oridonin, promotes the Fbw7-mediated proteasomal degradation of c-Myc, leading to subsequent cell growth inhibition and apoptosis and demonstrating a new c-Myc-_targeting strategy. Despite the effectiveness of molecular _targeting in cancer treatment, failure to achieve long-lasting efficacy with a single agent is observed because cancer cells can recover from oncogene addiction as a result of their genomic instability and heterogeneity. Combined cancer therapies were therefore developed and showed better efficacies than single-agent therapy in cancer cell lines and mouse models. Combined therapy based on c-Myc _targeting can be achieved through various strategies. Agents that also _target c-Myc but use different mechanisms, or agents that act on other genes in the c-Myc pathway, can be selected for combination. In addition, the _targeting of genes involved in different cellular processes in other pathways might also be a successful strategy. Regardless of the therapy adopted, it is important to first determine the molecular mechanisms underlying the agents to inform the therapy design. Among the various _targets of therapeutic agents is a family of noncoding small RNAs, called microRNAs, that have been implicated in the anti-cancer activity of many therapeutic agents. c-Myc, as a transcription factor, regulates the expression of many microRNAs and is in turn regulated by microRNAs. Combining c-Myc-_targeting agents with those that _target microRNAs might provide a novel approach for cancer therapy.

Cite this article as:

Huang Huilin, Weng Hengyou, Zhou Hui and Qu Lianghu, Attacking c-Myc: _targeted and Combined Therapies for Cancer, Current Pharmaceutical Design 2014; 20 (42) . https://dx.doi.org/10.2174/1381612820666140826153203