The enzyme target, Brk, is shown to be an accelerator of HER2-positive tumors

Tumor cells in a particular subset of breast cancer patients churn out too much of a protein called ErbB2 -- also often called HER2 -- which drives the cells to proliferate unchecked. Patients unlucky enough to be in this group -- about one in four -- have poorer prognoses and clinical outcomes than those who don't.

The drugs Herceptin and Lapatinib, prescribed in combination with other chemotherapeutic agents, have improved this picture significantly, but leave plenty of room for improvement: they suppress ErbB2 but are effective against less than half of ErbB2-producing tumors. Moreover, patients with tumors that do respond usually develop resistance to these drugs.

    In the perspective article in Nature Reviews Drug Discovery, the authors discuss the challenges facing drug discovery as intricate and numerous. They present a broad picture of drug discovery as three parts pertaining to targets, drugs, and patients. Targets for drug discovery are broken down into two classes, each of which is either essential or non-essential. Essential targets for drug discovery are targets that have essential function within all cells or a specific cell type. That means that the cell has to have this function operating or it will die. Non-essential targets are targets whose function can be lost and the cell will still survive. This concept can also be applied in terms of tissues as a target such as in breast tissue which is considered a non-essential tissue for life. Drugs that inhibit or block essential functions are likely to have narrow therapeutic windows. That is the drugs beneficial dose range is likely to be small before it becomes toxic such as 5-FUterm. 5-FU relies on the principle that cancer cells should be faster growing since they are growing out of control. 5-FU inhibits DNA synthesis, an essential function. Slow growing cells are not as affected as fast growing cells from 5-FU. This therapeutic windowterm is narrow and the consequences or side effectsterm of the narrow window is that 5-FU affects some of the naturally fast growing cells in the body, which is why hair loss is a common side-effect in 5-FU treatment.