Anticancer Drug Discovery — From Serendipity to Rational Design

Abstract

evidence of cancer dates back to several million years ago and has been found in fossilized remains (bones) of a dinosaur in Wyoming.The oldest specimens of cancer, a hominid malignant tumour (probably Burkitt's lymphoma) and bone cancer -were found in the remains of a body of either Homo erectus or an Australopithecus and in the remains of a female skull dating to the Bronze Age (1900-1600 B.C.), respectively.Bone cancers have been also discovered in mummies in the Great Pyramid of Giza and in mummified skeletal remains of Peruvian Incas.The earliest written records differentiating between benign and malignant cancers date back to ancient times (3000-1500 B.C., Mesopotamia and Egypt).Seven Egyptian Papyruses including the Edwin Smyth (2500 B.C.), Leyde (1500 B.C.), and George Ebers (1500 B.C.) described not only the symptoms but also the first primitive forms of treatment, i.e. the removal of a malignant tissue.The Hindu epic, the Ramayana (500 B.C.), mentioned not only cancer cases but also the first medicines in the form of arsenic pastes, for treatment of cancerous growth.Ancient Greek physician Hippocrates of Kos (ca.460-370 B.C.) described many different types of cancer (breast, uterus, stomach, skin, and rectum) recognised the difference between benign and malignant tumours and formulated the humoral theory of cancer genesis.As the veins surrounding the tumour resembled the crab claws, he named the disease after the Greek word carcinos.Cornelus Celsus (ca. 25 B.C.-50 A.D.), who described the first surgeries on cancers, translated Greek carcinos into now commonly used Latin term cancer.Claudius Galen (129-216 A.D.), the most famous Roman Empire physician, who wrote about 500 medical treatises, left a comprehensive descriptions of many neoplasms.He introduced the Greek word oncos (swelling) to describe tumours.Nowadays the use of Hippocrates and Celsus term is limited to describe malignant tumours, while Galen's term is used as a part of the name of the branch of medicine that deals with cancer -that is oncology.Followers of his works in Constantinople, Alexandria, Athens explained the appearance of cancer as a result of an excess of black bile.This idea prevailed through up to the 16 th century.The intensive studies in the field of anatomy and physiology during the Renaissance, resulted in advancement of surgery and development of rational therapies based on clinical observations.Based on autopsies William Harvey (1578-1657) described the systemic circulation of blood through the heart and body.Although cancers were still incurable, their temporary inhibition was often observed thanks to complementary remedies including the most common arsenic-based creams and pastes.In the beginning of the 16 th c.Zacutus Lusitani (1575-1642) and Nicholas Tulp (1593-1674) formulated the contagion theory and proposed isolation of patients in order to prevent the spread of cancer.Throughout the 17 th and 18 th centuries, this theory was so popular that the first cancer hospital founded in Reims, France, was forced to move outside the city.Nowadays, we know that their certain viruses, bacteria, and parasites can increase a risk of developing cancer.Gaspare Aselli (1581-1625), who discovered the lymphatic system, suggested a connection between the lymphatic system and cancer.Georg Ernst Stahl (1660-1734) and Friedrich Hoffman (1660-1742) proposed a concept that tumours grow from degenerating lymph constantly excreted by the blood.This idea was accepted by John Hunter (1728-1793), who described methods to identify surgically removable tumours.At that time the so-called humoral theory of cancer was replaced by the lymph theory.Claude-Deshasis Gendron (1663-1750) was convinced that cancer arises as a solid and growing mass untreatable with drugs, and must be completely removed.The discovery of a microscope by Drug Discovery