Analysis: We can expect to see more sophisticated and targeted metallodrugs designed to minimise side effects and overcome resistance
Cancer is known as the emperor of all maladies. The ever-increasing rise in the incidence of cancer has been attributed to prolonged life expectancy and mass lifestyle changes in the developing world. This disease was first described in Egypt dating back to approximately 1600 BC where the writing on papyrus read 'there is no treatment.'
Centuries later, despite widespread advances in medicine and cancer therapy, this disease is still one of the most prevalent causes of death in the developed world today. According to the World Health Organisation (WHO), cancer is defined as 'the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs'.
There are numerous types of cancer. The National Cancer Institute in the USA classifies cancer into six major types: carcinomas, sarcomas, myelomas, leukaemias, lymphomas and mixed types. The various types of cancer respond differently to treatment, and prognoses can vary widely. Cancer treatments include surgery, radiotherapy and most commonly chemotherapy. Typically, chemotherapeutic agents target rapidly dividing cells and both tumours and healthy multiplying cells are subject to the cell-killing effects of chemotherapy.
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From RTÉ Radio 1's Drivetime, delays in cancer treatments due to lack of funding
Medicinal inorganic chemistry has been practised for almost 5000 years. As far back as 3000 BC, Egyptians used copper to sterilise water. Gold was used in a variety of medicines in Arabia and China some 3500 years ago. In 1500 BC, various iron remedies were used, and around the same time zinc was discovered to have healing properties. In the past few centuries, silver has been used for the treatment of syphilis and magnesium for intestinal disorders.
There is no doubt that the discovery of the double helix structure of DNA (deoxyribonucleic acid) in 1953 triggered numerous studies into the biological processes behind different human diseases. At that time, drugs were mainly metal-free in nature, but approximately 50% of all cancer treatment plans are now platinum-based.
To date only three platinum drugs have received approval for worldwide clinical use, namely cisplatin, carboplatin and oxaliplatin. The toxicity of platinum drugs is attributed to their ability to bind DNA and cause cell death. Although they work well, these treatments have limitations due to strong side effects and the risk of drug resistance. The serendipitous discovery of the anti-cancer properties of cisplatin by Barnett Rosenberg in 1965 and its ability to bind DNA and cause cell death led to a renaissance in drug discovery with a particular focus on the use of metals as potential therapeutic agents.
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From RTÉ Radio 1's Morning Ireland, Prof Mark Lawler discusses the latest cancer statistics in Ireland, and where improvements are needed in care
Let’s imagine we are building structures with blocks. You can choose different types of blocks (like metal blocks) and each type has its own size, shape, and weight. By choosing different blocks, you can build structures with different characteristics. This is similar to how scientists can use different types of metals to create complexes with different properties like size, charge, and other physical and chemical properties.
Now, let’s think about adding stickers to our blocks. The type of sticker you add can change how your block interacts with other things. For example, a Velcro sticker might stick to fabric, while a magnet sticker might stick to metal. In the same way, changing the ligands (the ‘stickers’) attached to the metal complexes can change how they react and interact with important biological molecules like proteins, enzymes, and DNA.
Despite the diverse spectrum of metals with different properties investigated, the second most successful and efficient treatments after platinum were shown to be ruthenium-based chemotherapeutics. These complexes tend to be less toxic, and may act similar to iron in the body. In addition to platinum and ruthenium, to date, potential chemotherapeutics with titanium, rhodium, iridium, molybdenum, copper, and gold have also shown promise for the treatment of cancer.
The journey of metallodrugs, from the laboratory to the clinic, shows how research can advance healthcare and improve patient outcomes
Copper is one of the most promising candidates from the list for drug development due to its essential role in body, bioactivity, and oxidative nature. The toxicity of copper complexes is linked to their ability to produce free radicals, displace other metal ions, and directly break apart genetic material. Copper's role in tumour progression has led to the development of copper-specific compounds as therapies.
The unique chemical functionalities of these metal complexes offer opportunities for drug design, leading to a diverse portfolio of metallodrugs with different functions and mechanisms of action. Looking ahead, the future of cancer treatment is likely to be significantly influenced by the development and application of metallodrugs. As research progresses, we can expect to see more sophisticated and targeted metallodrugs, designed to minimise side effects and overcome resistance.
The use of nanotechnology could further enhance the delivery and effectiveness of these drugs. Moreover, the integration of metallodrugs with other treatment modes, such as immunotherapy and targeted therapy, could lead to more comprehensive and personalised treatment strategies.
While challenges remain, particularly in terms of drug design and understanding the precise mechanisms of action, the potential of metallodrugs in transforming cancer treatment is immense. The journey of metallodrugs, from the laboratory to the clinic, is a testament to the power of interdisciplinary research in advancing healthcare and improving patient outcomes.
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The views expressed here are those of the author and do not represent or reflect the views of RTÉ
