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Speaker | Anna Maria Halama, PhD
Affiliation | Weill Cornell Medicine, Qatar
Advancing cancer treatment by targeting dysregulated metabolism – A roadmap
Cancer has been considered a metabolic disease, given that tumor growth and metastatic progression strongly depends on adapted cell metabolism. We and others showed that cancer cells adjust metabolic program to their specific energy needs in response to challenging micro environment, which frequently results in cancer cell “addiction” to certain metabolic pathways. Those “addictions” could be deployed as treatment targets. However, cancer cell under treatment acquires metabolic flexibility enabling dynamic switches between metabolic pathways which leads to cancer survival and to development of the resistance mechanisms. Thus, on one hand in depth understanding of metabolic dependences of cancer cells at different stages of progression is critical for identification of treatment targets.
On the other, probing those targets along with chemotherapeutics can further result in identification of switches through which cancer cell acquires metabolic flexibility and obtains resistance. Metabolic profiling by providing quantitative measure of metabolic processes offers attractive strategy for investigation of not only cancer cells “addictions” but also metabolic switches contributing to treatment resistance. A series of in vitro and in ovo experiments deploying metabolic analysis was conducted to further understand mechanisms of cancer cell resistance. Responses of cancer cells to standard chemotherapeutics as well as treatment targeting their metabolic “addictions” were monitored. The metabolic and molecular mechanisms contributing to cancer cell survival under the treatment were identified along with metabolic switches which were proposed as novel treatment targets.
Taken together, metabolic dysregulations monitored under cancer cell exposure to various drugs lead to identification of molecular changes in cancer cell and thus can serve as a roadmap for establishment of novel combined treatment strategies. Yet, significant effort must be put towards translation of the findings into the clinical setting as well as implementation of metabolomics into standard clinical pipeline especially for complex diseases such as cancer.
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