File:Fphar-04-00028-g001.jpg

English: FIGURE 1. A MAJOR IMPEDIMENT IN THE TREATMENT OF CANCER IS THE DEVELOPMENT OF RESISTANCE. While most tumors initially respond to the given therapy, the majority will relapse following treatment, and in some cases resistance even predates clinical intervention. Therefore cancer resistance can be classified in to two broad classes: primary or acquired. In both cases, the emergence of resistant cells could be due to, at least, two mechanisms: (A) presence of multiple initial clones some of which emerge as dominant after treatment. These subpopulations could possess stem-like characteristics and/or use their interactions with the surrounding microenvironment to enter into a dormant state, thus surviving the insult of therapy. (B) Acquisition of stochastic alterations within the cancer cells per se. In all cases, the surviving population is less likely to respond to any further therapy and will be responsible for the minimal residual disease and cancer relapse. The biochemical underpinnings of resistance include: alterations to drug metabolism, increased drug efflux, decreased drug uptake, modification of the drug targets, amplification of targeted protein, genetic rewiring, enhanced DNA repair, inactivation of apoptotic proteins, or activation of anti-apoptotic ones, among others.