Platinum-based antineoplastic

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

s (informally called platins) are

chemotherapeutic Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

agents used to treat

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

. They are

coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...

es of

platinum Platinum is a chemical element with the symbol Pt and atomic number 78. It is a dense, malleable, ductile, highly unreactive, precious, silverish-white transition metal. Its name originates from Spanish , a diminutive of "silver". Pla ...

. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

, commonly used drugs include

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelio ...

oxaliplatin Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by injection into a vein. Common side effects include numbness, feeling ti ...

, and

carboplatin Carboplatin, sold under the trade 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 ...

, but several have been proposed or are under development. Addition of platinum-based chemotherapy drugs to chemoradiation in women with early

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

seems to improve survival and reduce risk of recurrence. In total, these drugs can cause a combination of more than 40 specific side effects which include

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

, which is manifested by

peripheral neuropathies Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

including

polyneuropathy Polyneuropathy (poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands ...

Mechanism of action

As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause

crosslinking of DNA 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 stra ...

as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of

guanine Guanine () (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is c ...

, forming a 1, 2 intrastrand crosslink. The resultant crosslinking inhibits

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

and/or

DNA synthesis DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occur ...

. Platinum-based antineoplastic agents are sometimes described as "alkylating-like" due to similar effects as

alkylating antineoplastic agent An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA. The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring. Since ca ...

s, although they do not have an

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloal ...

group.

Examples

Strategies for improving platinum-based anticancer drugs usually involve changes in the neutral

spectator ligands In coordination chemistry, a spectator ligand is a ligand that does not participate in chemical reactions of the complex. Instead, spectator ligands (vs "actor ligands") occupy coordination sites. Spectator ligands tend to be of polydentate, such th ...

, 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 Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal o ...

has been explored to deliver platinum more efficiently in the case of

lipoplatin Lipoplatin (Liposomal cisplatin) is a nanoparticle of 110 nm average diameter composed of lipids and cisplatin. This new drug has successfully finished Phase I, Phase II, and Phase III human clinical trials. It has shown superiority to cisplat ...

, which is introduced into the tumor sites thereby reducing the chance of toxicity.

Cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelio ...

was the first to be developed.

is particularly effective against

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an ...

; the cure rate was improved from 10% to 85%. Similarly, the addition of cisplatin to adjuvant chemotherapy led to a marked increase in disease-free survival rates for patients with

medulloblastoma Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa. The brain is divided into two ...

- again, up to around 85%. This application of cisplatin was developed by pediatric oncologist Roger Packer in the early 1980s. File:Cisplatin-stereo.svg,

File:Carboplatin-skeletal.svg,

File:Oxaliplatin-2D-skeletal.png,

File:Nedaplatin.png,

nedaplatin Nedaplatin ( INN, marketed under the tradename Aqupla) is a platinum-based antineoplastic Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platin ...

File:Triplatin tetranitrate.svg,

triplatin tetranitrate Triplatin tetranitrate ( rINN; also known as BBR3464) 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 repli ...

File:Phenanthriplatin.png,

phenanthriplatin Phenanthriplatin or ''cis''- t(NH3)2-(phenanthridine)ClO3 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. ...

, a proposed new anticancer drug. File:Picoplatin.png,

picoplatin Picoplatin is a platinum-based antineoplastic agent in clinical development by Poniard Pharmaceuticals (previously NeoRx) for the treatment of patients with solid tumors. In Phase I and Phase II clinical trials, picoplatin demonstrated activity ...

, which remains in trials File:Satraplatin.svg,

satraplatin Satraplatin (International Nonproprietary Name, INN, codenamed JM216) 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 ...

References

{{Intracellular chemotherapeutic agents Medicinal inorganic chemistry Platinum compounds Chemotherapy