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A second example is the utilization of thalidomide, lenalidomide, and pomalidomide for treatment of leprosy and various cancers. After the infamous and tragic history of thalidomide, it would be nearly impossible for any researcher in a big pharmaceutical venture to revive this drug. Being approved in Germany in 1957, thalidomide was frequently used for treatment of morning sickness. As the side effect profile seemed very favorable, it was frequently used by pregnant women. However, in 1961 reports on increased birth defects were reported, which were finally linked to thalidomide. These defects led to a significantly increased mortality at birth as well as to limb deformations, heart problems, and other side effects. It is estimated that more than 10 000 children were born with limb defects. The retraction of the drug from the European market led to introduction of a requirement for more stringent characterization of drug safety during the registration process. Teratogenicity is now one of the flags that will lead to exclusion of a drug from almost any optimization program, as it is difficult to rule out any erroneous use in women of child‐bearing age. However, by 1964, only three years after market withdrawal, Jacob Sheskin from Hadassah University in Jerusalem used thalidomide to treat patents in serious condition of leprosy [9]. In his original publication, Sheskin referred to administering thalidomide to six leprosy patients as a sedative drug; however, to his surprise the disease condition of all six patients improved. The initial study was followed by multiple comparative studies and the clinical benefit, in particular with respect to onset of action, and good tolerability became evident. Thalidomide was finally approved for treatment of leprosy in 1998.

Further research by Judah Folkman's laboratory at Children's Hospital at Harvard Medical School demonstrated that thalidomide effectively inhibited angiogenesis induced by fibroblast growth factor 2, offering a potential mechanistic explanation for the observed limb deformations [10]. Angiogenesis, however, is a hallmark of tumor growth, so in 1997 a trial was started [11] to examine the efficacy of treatment with thalidomide in patients with multiple myeloma, a hematological cancer that was not curable by conventional chemotherapy. A response rate of 32 % was observed. Actually, a first oncology clinical trial of thalidomide had already been performed as early as 1965. Olsen et al. [12] treated 21 patients suffering from various types of advanced cancers with thalidomide. Overall no inhibitory effect of tumor progression was observed in this study. The authors described subjective palliation in one third of patients. Albeit no tumor regression was observed, the authors noted a possible temporary slowing of rapidly progressing cancer in two patients. Interestingly, one of them was suffering from multiple myeloma.