Cancer is a major public health problem in the United States and throughout the world. It is currently the second leading cause of death in the United States and is expected to surpass heart diseases in the next few years to become the leading cause of death [1]. The estimated number of new cases of invasive cancer (all types) in the United States is 1,658,370 which is equivalent of more than 4,500 new cancer diagnoses each day. In addition, the estimated number of deaths from cancer in 2015 is 589,430 corresponding to about 1,600 deaths per day [1]. Though there has been a steady increase in survival for most cancers the death rate remains unacceptable and for certain cancers i.e. lung and pancreatic cancers the 5-year relative survival is currently 18% and 7%, respectively. Traditional chemotherapy drugs act against all actively dividing cells (normal and cancerous cells) whereas targeted cancer therapies are drugs that interfere with specific molecular targets involved in cancer cell growth, progression and spread of cancer. Most targeted therapies are either small molecules or monoclonal antibodies. However, therapeutic strategies that target single molecular pathways eventually succumb to problems of intrinsic or acquired resistance due to extensive signaling "cross talk". Thus, combination targeted therapies are more attractive, as they synergistically inhibit multiple receptors. However, overlapping toxicities and pharmacological interactions limit patient compliance, feasibility and efficacy. Clearly, there is an urgent need to develop new first-line agents with enhanced efficacy and reduced toxicity. We support the concept that the ideal drug maybe a broad spectrum drug whose efficacy is based not on the inhibition of a single target but rather a multi-targeted drug that affects several proteins or events that contribute to the etiology, pathogenesis and progression of diseases [2]. In addition, multi-pathway targeting is one of the strategies to overcome chemo-resistance. To design novel anticancer drugs with unique structural properties we have taken an innovative and nontraditional approach where we combine pharmacophoric components to create new and highly potent small molecules with a simple three component "A-B-C" structure where each pharmacophore is known to have anticancer properties on its own or when incorporated as a component of an existing drug. Our multi-component "A-B-C" drugs can target simultaneously two or more different molecular targets or molecular mechanisms in a single entity which should reduce the likelihood of drug resistance.
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