Is There a Therapeutic Window for Metabolism-Based Cancer Therapies?

Cells that have undergone an oncogenic transformation have an altered metabolism compared to the cells they originate from (1). This observation led to the addition of “a deregulated metabolism” to the hallmarks of cancer (2). Accordingly, it has been extensively demonstrated that many of the observed alterations in the metabolism of cancer cells are important for their proliferation (1, 3, 4). However, a metabolic alteration that is important for cancer cell proliferation is not automatically a good target for treatment, as treatments also have to be selective toward cancer cells. Since almost all of the cancer-induced metabolic changes are not caused by gain of function mutations in specific enzymes, metabolism-based drug have to be developed against the naturally occurring enzymes. Thus, the valid question arises whether there is a therapeutic window for targeting the deregulated metabolism of cancer cells. In the following, I would like to describe the challenges and advocate the opportunities for metabolic drug targets in cancer treatment. In the first section, I will address the question whether there is in general a therapeutic window for metabolism-based cancer treatment, while in the second section, I will discuss new concepts that can refine metabolism-based anticancer strategies.