Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of chemotherapy, commonly used drugs include cisplatin, oxaliplatin, and carboplatin, but several have been proposed or are under development. [1] Addition of platinum-based chemotherapy drugs to chemoradiation in women with early cervical cancer seems to improve survival and reduce risk of recurrence. [2]
In total, these drugs can cause a combination of more than 40 specific side effects which include neurotoxicity, which is manifested by peripheral neuropathies including polyneuropathy. [3]
As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause crosslinking of DNA as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of guanine, forming a 1, 2 intrastrand crosslink. [4] [5] The resultant crosslinking inhibits DNA repair and/or DNA synthesis. This mechanism leads to specific patterns of damage in DNA, which can kill cancer cells but can also increase the risk of secondary tumors developing. [6]
Platinum-based antineoplastic agents are sometimes described as "alkylating-like" due to similar effects as alkylating antineoplastic agents, although they do not have an alkyl group. [7]
Strategies for improving platinum-based anticancer drugs usually involve changes in the neutral spectator ligands, changes in the nature of the anions (halides vs various carboxylates), or changes in the oxidation state of the metal (Pt(II) vs Pt(IV)). Nanotechnology has been explored to deliver platinum more efficiently in the case of lipoplatin, which is introduced into the tumor sites thereby reducing the chance of toxicity. [8]
Cisplatin was the first to be developed. [9] Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%. [10] Similarly, the addition of cisplatin to adjuvant chemotherapy led to a marked increase in disease-free survival rates for patients with medulloblastoma - again, up to around 85%. [11] This application of cisplatin was developed by pediatric oncologist Roger Packer in the early 1980s. [12]
Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.
Cisplatin is a chemical compound with formula cis-[Pt(NH3)2Cl2]. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. It is given by injection into a vein.
Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication used to treat colorectal cancer. It is given by injection into a vein.
Nitrogen mustards (NMs) are cytotoxic organic compounds with the bis(2-chloroethyl)amino ((ClC2H4)2NR) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents.
Busulfan is a chemotherapy drug in use since 1959. It is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Its chemical designation is 1,4-butanediol dimethanesulfonate.
Altretamine, also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.
Triplatin tetranitrate is a platinum-based cytotoxic drug that underwent clinical trials for the treatment of human cancer. The drug acts by forming adducts with cellular DNA, preventing DNA transcription and replication, thereby inducing apoptosis. Other platinum-containing anticancer drugs include cisplatin, carboplatin, and oxaliplatin.
In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. These crosslinks can, however, be repaired through excision or recombination pathways.
An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA.
Satraplatin is a platinum-based antineoplastic agent that was under investigation as a treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
Nedaplatin is a platinum-based antineoplastic drug which is used for cancer chemotherapy. The complex consists of two ammine ligands and the dianion derived from glycolic acid.
Semustine is an alkylating nitrosourea compound used in chemotherapy treatment of various types of tumours. Due to its lipophilic property, semustine can cross the blood-brain barrier for the chemotherapy of brain tumours, where it interferes with DNA replication in the rapidly-dividing tumour cells. Semustine, just as lomustine, is administered orally. Evidence has been found that treatment with semustine can cause acute leukaemia as a delayed effect in very rare cases.
Stephen James Lippard is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of nonliving substances such as metals with biological systems. He is also considered a founder of metalloneurochemistry, the study of metal ions and their effects in the brain and nervous system. He has done pioneering work in understanding protein structure and synthesis, the enzymatic functions of methane monooxygenase (MMO), and the mechanisms of cisplatin anticancer drugs. His work has applications for the treatment of cancer, for bioremediation of the environment, and for the development of synthetic methanol-based fuels.
Chemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy. CIPN afflicts between 30% and 40% of patients undergoing chemotherapy. Antineoplastic agents in chemotherapy are designed to eliminate rapidly dividing cancer cells, but they can also damage healthy structures, including the peripheral nervous system. CIPN involves various symptoms such as tingling, pain, and numbness in the hands and feet. These symptoms can impair activities of daily living, such as typing or dressing, reduce balance, and increase risk of falls and hospitalizations. They can also give cause to reduce or discontinue chemotherapy. Researchers have conducted clinical trials and studies to uncover the various symptoms, causes, pathogenesis, diagnoses, risk factors, and treatments of CIPN.
Phenanthriplatin or cis-[Pt(NH3)2-(phenanthridine)Cl]NO3 is a new drug candidate. It belongs to a family of platinum(II)-based agents which includes cisplatin, oxaliplatin and carboplatin. Phenanthriplatin was discovered by Professor Stephen J. Lippard at Massachusetts Institute of Technology and is currently being developed by Blend Therapeutics for its potential use in human cancer therapy.
Dicycloplatin is a chemotherapy medication used to treat a number of cancers which includes the non-small-cell lung carcinoma and prostate cancer.
Lobaplatin is a platinum-based antineoplastic metallodrug approved exclusively in China for the treatment of small cell lung cancer, inoperable metastatic breast cancer and chronic myelogenous leukaemia. The drug is a third-generation analogue of cisplatin, the first globally approved and widely used platinum-based anticancer drug.