Introduction
Despite undeniable advancements in early diagnostics and progress in reducing morbidity through therapeutic efforts, it appears that after spending billions of dollars on oncology research since 1971, more than three decades later the ‘war on cancer’ is still far from being won (http://dtp.nci.nih.gov/timeline/noflash/milestones/M4_Nixon.htm).
Molecularly targeted therapy represents the major hope to substantially improve survival of cancer patients. The principle of this therapy is fundamentally important: blocking with agents deregulated downstream signalling pathways which increase cell proliferation and survival and prolong cell death (apoptosis) may result in effective cancer treatment.
Indeed, pharmaceutical industry and academia research efforts have led to the development of targeted agents which are tested in clinical trials. Over the last 10 years, there has been an explosion of interest in targeted agents for the treatment of cancer. Despite the standardization of surgery, radiotherapy and empirical chemotherapy, millions of people die from cancer, according to US and world statistics data [1, 2]. The future is predicted to be even worse, with cancer expected to be the top health problem in the developed world. With the aging population, a steadily worsening environment and climate changes, an increase of 55% is estimated for 2020 [3].
There are two ways to alter this situation:
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• Primary prevention and early detection through screening programs; |
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• Once diagnosis has been established, in order to improve efficacy with lower or better-tolerated toxicity, biologically targeted drugs are added to the current standard treatment. |
This perspective article discusses whether basic scientific discoveries have met expectations regarding their translation into successful clinical treatment for solid cancer. Moreover, this article describes whether and how biomedical approaches should change and move away from single protein-coding genes to causal networks-prediction approaches and from a ‘one-size-fits-all’ approach to personalized biomedicine.
Agents targeting the heart of tumors may avoid toxicity and increase efficacy by focusing their action on the genetic abnormalities that cause cells to grow uncontrollably, without influencing normal cells. This may avoid the toxic effects often observed in traditional chemotherapy treatments while simultaneously increasing the anticancer efficacy. This new generation of systemic drugs, administered either in addition to empirical chemotherapy or alone, has received great enthusiasm. This optimism in the early 2000s was primarily based on the clinical success of, initially, tamoxifen – the first generation of targeted agents – and, more recently, trastuzumab in the treatment of breast cancer.
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