Stem cells are one of the most fascinating areas of biology today. Knowledge in this field has advanced in the area of healthy cell replacement of damaged cells and in the area of the development of an organism from a single cell, a promising area of science leading scientists to investigate the possibility of cell-based therapies to treat disease. Scientists have hypothesised that stem cells may be the basis of treating diseases like Parkinson's disease, diabetes, and heart disease. As scientists learn more about stem cells, it may become possible to use the cells not just in cell based therapies, but also for screening new drugs and toxins and understanding birth defects. However, human embryonic stem cells have only been studied since 1998. For treatments to be developed studies should be made of how stem cells remain unspecialized and self renewing for many years, and on identifying the signals that cause stem cells to become specialized cells.
It has taken scientists 20 years to learn how to grow human embryonic stem cells in the laboratory after the specific factors and conditions that allow stem cells to remain unspecialized were identified. An important area of research is understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed for repair of a specific tissue. Such information is critical for scientists to be able to grow large numbers of unspecialized stem cells in the laboratory for further experimentation.
Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions is critical because the answers may lead scientists to find new ways of controlling stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes including cell-based therapies.
Differential response to the same drug in different patients is a common clinical experience. Many different factors may contribute to differential response including variable age and body size, diet, gastro-intestinal absorption, compliance with therapy and characteristics of the drug target. Understanding the variable response to drugs seems particularly pressing in the field of oncology, in which the stakes are high, drugs commonly have a narrow therapeutic index, and toxicities can be severe. Significant heterogeneity in the efficacy and toxicity of chemotherapeutic agents is observed within cancer populations. Pharmacogenetics (PGx) is the study of inheritance in interindividual variation in drug disposition. The allure of pharmacogenetics, in the treatment of cancer patients, comes from the potential for individualisation of cancer therapy, minimizing toxicity, while maximizing efficacy. Ideally, routine management of patients would include analysis of their single nucleotide polymorphism linkage disequilibrium (SNP-LD) profile prior to treatment, allowing stratification of patients into treatment groups, thus individualising their therapy.
Epidermal growth factor receptor (EGFR)-targeted therapies have demonstrated remarkable success in a small subset of non-small cell lung cancer patients. The mechanism of response has been an area of active research, with somatic mutation in a number of genes in the EGFR signal transduction pathway and copy number alterations of genes of the EGFR family as candidates contributing towards response. Continuing studies should help determine an appropriate biomarker or combination of biomarkers that can be used to predict response to this class of therapy.
Increased knowledge of the mechanistic properties of malignant growth has facilitated the development of molecular-based therapies that can act on specific targets. With molecular-targeted therapies, maximum antitumor effects may be achieved at doses that are considerably below the maximum tolerated dose. Adverse events are mild, manageable, and reversible on treatment cessation. Collectively, these findings support the use of targeted agents for improving the clinical outcomes and quality of life in patients with advanced NSCLC. These agents should be considered as a treatment option for patients who have failed or are ineligible for traditional chemotherapy.
These observations suggest that as pharmacogenetics moves forward with ever more powerful genome-wide technologies, the field will benefit from a cautious approach to describing applications that are still in the future; "personalized medicine for all" is not on the immediate horizon, more a distant goal. A systematic approach to the dissection of important metabolic pathways using a combination of strategies and determining the applicability and clinical importance of the knowledge gained will move us toward this goal.42 Surrogate endpoints such as minimal residual disease or pharmacodynamic endpoints may provide earlier data than waiting for a large randomized trial to mature and allow greater focus on single drugs within a complex therapeutic strategy.