The Concept of Personalized Cancer Medicine with Natural Products

Assays to predict the response of tumors towards chemotherapy are relevant for custom-tailored, individualized therapies. Clinically, chemotherapy is frequently hindered by drug resistance. Since most established cytostatic drugs lack sufficient tumor specificity, normal tissues are also affected by severe side effects. Novel strategies to broaden the narrow therapeutic range by separating the effective dose and toxic dose would be of great benefit for the patients.

Whereas the statistical probability of therapeutic success is well-known for larger groups of patients from clinical therapy trials, it is, however, not possible to predict how an individual tumor will respond to therapy. Although clinicopathological factors (tumor size, lymph node and far distance metastases) are of prognostic relevance for larger cohorts, they are less helpful predicting treatment success or side effects in individual patients. Therefore, efforts have been undertaken to predict drug response in vitro. The idea is to determine sensitivity or resistance beforehand to subsequently choose the clinically most effective treatment for each individual patient. The advent of molecular biology paved the way for the genetic characterization of drug-resistant tumors. Still, the transfer of these techniques from the bench to the bed is an unfulfilled requirement. Nevertheless, current progress gives reason to believe that molecular approaches will significantly improve individual tumor therapy.

We present experiences with predictive chemosensitivity testing of the past two decades. We span a bow from relevant cytotoxicity assays, immunohistochemical detection of prognostic markers for therapy response of tumors and survival time of patients to modern pharmacogenomic techniques (comparative genomic hybridization, DNA methylation arrays, mRNA and micro-RNA expression arrays etc.). Our own data obtained by these methods will be compared to clinical data of patients. We will present results for the prediction of sensitivity and resistance both to classical anticancer drugs as well as to phytochemicals and medicinal herbs. The presented techniques also possess relevance for phytotherapeutic drugs such as mistle toe preparations, which are already well established in clinical routine therapy. References: [1] Volm M, Koomägi R, et al. (2008) Clin Cancer Res 8: 1843–1848. [2] Gillet JP, Efferth T, et al. (2004) Cancer Res 64: 8987–8993. [3] Efferth T, Konkimalla VB, et al. (2008) Clin Cancer Res 14: 2405–2412. [4] Li PC, Lam E, et al. (2008) Cancer Res 68: 4347–4351. Efferth T (2010) Planta Med 76: 1143–1154.