Precision cancer medicine: where to target?

The discovery of the first oncogene Src in 19761 opened up the field of molecular oncology and led to the discovery of oncogenes and anti-oncogenes that are involved in the formation and progression of cancers2. Nearly 4 decades of research on the functions and molecular mechanisms of oncogenes and anti-oncogenes and the related cell growth signaling pathways, has led to the understanding that cancer is characterized by uncontrolled cell growth that is regulated by multiple growth factors, growth factor receptors, cytoplasmic growth signal transducers and nuclear transcription factors, which collectively control nucleotides synthesis, DNA replication and cell division. Cancer treatments have been developed to target both the growth regulatory mechanisms as well as the DNA replication/cell division machinery. The traditional chemotherapies mostly target the cell division machinery, including nucleotide metabolism, DNA replication and cell division3,4. While such traditional chemotherapies are effective in killing cancer cells and blocking cancer cell growth, they suffer from the lack of targeting specificity as they are equally toxic to normal dividing cells, which are commonly present in the bone marrow, digestive tract and hair follicles. As a result, they result in severe side-effects such as myelosuppression, mucositis and hair loss. On the other hand, targeted cancer therapies, which are designed to attack the growth regulatory systems, particularly the genetically mutated and misbehaved specific cell growth pathway control molecules, have become increasingly popular in the past two decades. The targeted therapies have been proven to be more effective and less harmful to normal cells than the traditional cytotoxic or cytostatic chemotherapies, because the targeted molecules and their mutations are cancer cell-specific.