Chapter 1 - Definition: Translational and Personalised Medicine, Biomarkers, Pharmacodynamics
Conclusions and Future Directions
The sequencing of the human genome and of many solid tumours has identified key genetic alterations and has provided insight into the biological mechanisms involved in oncogenesis. At the same time, advances in molecular biology and histopathology techniques have enabled more detailed characterisation of tumour tissues. Elucidation of important signalling mechanisms deranged in cancer has led to the identification of new drug targets, enabling the development of novel therapies. The use of biomarkers has facilitated the selection of patients who would derive the most benefit from systemic therapy and a more personalised approach to treatment. However, only a few biomarkers for common solid tumours are currently routinely tested in the clinical setting. In the future, the development of less expensive and high-throughput sequencing methods will allow for the expansion of testing for genetic alterations to all tumours and patients and will lead to more tailored therapies. New and less invasive methods for obtaining tumour material such as measurement of circulating tumour cells in peripheral blood will enable more frequent monitoring of tumour response to therapy. Patients will benefit from this individualised approach to cancer care by receiving therapies modified to their unique molecular and cellular characteristics, leading to an improved therapeutic benefit to toxicity ratio. Ongoing biomarker development will allow the oncologist not only to better define prognosis and predict treatment response but also provide an early indicator of treatment efficacy.
A greater understanding of the pharmacodynamic effects of drugs and the use of surrogate biomarkers will also aid clinicians in identifying patients who are not responding to standard therapies and may therefore need a different treatment approach. Additional research is needed to develop new biomarkers to better select patients suitable for specific therapies, to monitor treatment response, and to identify patients at greater risk of toxicities. The incorporation of novel biomarkers in phase I clinical trials may also improve the efficacy of experimental drug testing, through the early identification of patients likely to respond to a new treatment for enrichment in phase II/III trials.
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