platinum , ruthenium , rhodium , and iridium ( platinum group metals ) and gold together with silver ( copper group metals ) are known as noble metals . we discuss the ones that are already used in oncology or have a therapeutic potential . platinum ( pt ) , with atomic number 78 , atomic mass 195.08 , density 21.45 g / cm , and melting point 1772c , is quite rare in nature and usually is found together with ruthenium , rhodium , and palladium . in chemical compounds it is mainly found in its oxygenation state of ii , iii , iv , and vi ; it has very good properties of electric and thermal conductivity . platinum was first found in columbia in 1735 , named from the spanish  platinum  , meaning  small silver  because of its relative lack of usefulness compared to silver , which is called in spanish  plata  . platinum is mined in russia , in the republic of south africa , canada , and in the usa . rosenberg et al .   used cisplatin firstly for the suppression of escherichia coli growth . the most commonly used cytostatics from this group are cisplatin , carboplatin , and oxaliplatin ( used from 1978 , 1980 , and 1988 , respectively ) . they are used in the therapy of many malignant tumours : ovarian cancer , testicular cancer , lung cancer , oesophageal cancer , stomach cancer , prostate cancer , bladder cancer , squamous cell carcinoma of head and neck , cervical cancer combined with radiotherapy , colorectal cancer and non - hodgkin lymphoma , multiple myeloma , neuroblastoma , melanoma , and mesothelioma . cisplatin is built from one atom of platinum , two chloride ions , and two molecules of ammonia . carboplatin has one atom of platinum , two molecules of ammonia , and a cyclobutanedicarboxyl ligand with oxygen atom from the carboxyl group . oxaliplatin , however , is a complex compound of platinum with 1,2-diaminocyclohexane and an oxalate group . the addition of new ligands to platinum atom has been done with the aim of breaking chemoresistance to platinum compounds , which is observed during therapy . this may be a result of the quantity and type of new dna adducts and also of the reduction of treatment side effects [ 4 , 5 ] . cytostatics that are platinum derivatives are alkylating agents . by making stable cross bindings with dna ( bonds with nucleophilic nitrogen atom n7 of two neighbouring guanines ) dna replication the change of dna structure is recognised by specific proteins , including the hmsh2 protein form the high mobility group ( hmg ) , and may cause damage repair ; other proteins may be a signal triggering apoptosis [ 69 ] . gong et al .   found that cisplatin may also induce cell death in parallel by activation of suppressor protein p53 and protein p73 . there is , however , evidence that there are other ( independent from p53 cell death ) pathways in cisplatin based therapies . cisplatin induces activation of the c - abl tyrosine kinase , which may induce proapoptotic protein p73 [ 1114 ] . according to the information enclosed with the drug , the most common side effects ( more than 1 out of 10 patients ) after cisplatin treatment are : leukopenia , thrombocytopenia , anaemia , hypernatremia , impairment of hearing , decreased appetite , nausea , diarrhoea , kidney malfunction , and fever . in more than 1 out of 100 patients but in less than 1 out of 10 patients peripheral neuropathy side effects of carboplatin include kidney damage ( less often than cisplatin ) , alopecia , fatigue , and elevated liver enzyme activity . oxaliplatin causes peripheral neuropathy , fatigue , hypernatraemia and hypokalaemia , anaemia , thrombocytopaenia , and leukopaenia . gold ( au ) , with atomic number 79 , atomic mass 197.0 , density 19.3 g / cm , and melting point 1063c , is found in its free state and in minerals . in chemical compounds it is mainly in oxygenation states i and iii ; it has very good properties of electric and thermal conductivity . the history of gold mining is more than 6000 years old , its colour and timeless value were well known in art and architecture of ancient civilisations . the main producer of gold is the republic of south africa , although it is also mined in other regions of the world . its complex auranofin is used in rheumatism treatment , and its anticancer potential is also described in both in vitro and in vivo models [ 1517 ] . in recent years nanotechnology using structures of 1 nm to 150 nm also involves the use of gold . gold particles are stable and non - toxic ; they can bind drugs , antibodies , or antigens , they can have transport and active substance release capability . they are safe for healthy tissues because they do not disintegrate during transport [ 15 , 18 , 19 ] . they reduce tumour mass also in platinum - resistant cancers , and they have lower toxicity , especially for the kidneys [ 2022 ] . the anticancer activity of gold complexes is not known , although some research shows that they may have inhibiting activity towards enzymatic protein complexes like thioredoxin ( trx ) and thioredoxin reductase ( trxr ) ; they may also inhibit proteasome activity  a mechanism linked with carcinogenesis [ 15 , 2327 ] . thioredoxin and thioredoxin reductase protect the cell from reactive oxygen species and apoptosis , and they are involved in cell growth and proliferation . it is one of the factors that is linked to cell chemoresistance ; it is also linked to cells invasive and metastatic potential . thioredoxin also causes expression of hypoxia - induced factor 1 ( hif-1 ) and increases production of protein products from the vegf gene promoting neoangiogenesis in tumours [ 15 , 28 , 29 ] . thioredoxin and thioredoxin reductase are found in two forms : cytoplasmic and mitochondrial ( trxr1 and trxr2 ) . gold complexes inhibit thioredoxin reductase in mitochondria by reducing membrane potential , leading to apoptosis [ 15 , 21 ] . it is thought that the enzymatic complex of thioredoxin  thioredoxin reductase can be a target in cancer therapy [ 26 , 28 ] . this is a complex responsible for degradation of ubiquitin marked proteins that may cause selective apoptosis of cancer cells [ 16 , 20 ] . stat pathway is a transcription activator that plays a role in proliferation and has an antiapoptotic effect on cancer cells . recent research has shown evidence anticancer activity of gold complexes both in vitro and in vivo . it was proven that auranofin in human ovarian cancer cell lines induces apoptosis by inhibition of thioredoxin reductase ; it was also proven on cisplatin - resistant cell lines . a similar action of gold ( iii ) complex was observed on human ovarian cancer stem lines , and in one study it was compared with cisplatin and oxaliplatin . antiproliferative and proapoptotic actions of gold complexes were stronger than those of platinum derivatives . in another study gold complexes were assessed for their antiproliferative potential in ovarian cancer cell lines and embryonic cell lines a study on human breast cancer showed that the use of auranofin also has an anticancer effect ; the inhibition mechanism was linked to the stat pathway and telomerase . it was found that the effectiveness of pegylated gold nanoparticles ( aunps ) combined with docetaxel on prostate cancer cell lines was 50%  only half of cells survived , others were damaged . an even higher effectiveness of gold nanoparticles was observed in xenograft of human prostate cancer in mice with the use of particles having gold au isotope . gold nanoparticle complex was developed , and this complex was linked to the cetuximab antibody and gemcitabine , which was administered to animals that had hepatocellular carcinoma ( hcc ) heterografts . heterografts entered apoptotic pathway , they were found to be necrotic , their proliferative potential was diminished , and healthy tissues were not damaged . an interesting study on auranofin use in transgenic mice with chronic lymphocytic leukaemia ( cll ) was made . this type of leukaemia has a high remission rate after first - line chemotherapy , although relapses are linked to chemoresistance . it seems that gold complexes and nanoparticles , because of their anticancer activity , will find their way into clinical trials , not only experimental models . argentum ) , with atomic number 47 , atomic mass 107.86 , density 10490 kg / m , and melting point 961.78c , is found in nature in its free state and in minerals like argentite . it is a silver - white metal , with very good thermal and electrical conductivity . greeks coated plates and cups with silver to stop disease spreading , and they put silver coins into water buckets to extend the water 's freshness . they also gave silver spoons to children for sucking , which was believed to protect them from illnesses . the very first silver compound that was used for treatment was silver nitrate , which was discovered by basilius valentinus back in the 15 century . in the 19 century , for the first time , 0.2% solution of silver nitrate was used for burn wound care . in 1874 t. billroth proved the antiseptic properties of silver by using its antibacterial effect on staphylococcus aureus . later on the antibacterial properties of silver were proven against the following bacteria : streptococcus , pseudomonas and escherichia . in the early 1990s it was observed that people with low concentrations of silver as a trace element often undergo bacterial , viral , or fungal infections . nowadays many surgical instruments are silver coated , as well as other instruments like dialysis catheters . everywhere where risk of infection is present , silver can be used . in the last few years oncological research the first report of the cytotoxic effect of silver nanoparticles ( agnps ) was proven against mcf-7 breast cancer cell line in 2013 . kathiravan   used the extract of melia dubia leaves ( a tree growing in india ) , and sathishkumar   used extract from dendrophthoe falcata . silver nanoparticles developed in this way were proven to have an anticarcinogenic effect on mcf-7 breast cancer cell line . vasanth , with the use of agnps , stopped replication of a cervical cancer cell line ( hela ) by induction of apoptosis . to produce silver nanoparticles he used extract from the bark of moringa oleifera . chinese researchers have proven the cytotoxic effect of silver nanoparticles against aml ( acute myeloid leukaemia ) cell lines such as shi-1 , thp-1 , dami . he proved that those complexes inhibit proliferation by inducing cell cycle cessation in phase g1 and s in hepatocellular carcinoma cell line ( hepg2 ) . he observed in vivo tumour reduction when a silver nanoparticle was combined with alisertib ( selective kinase inhibitor ) . iridium ( ir ) , with atomic number 77 , atomic mass 192.217 , density 22.56 g / cm , and melting point 2466c , is found in nature as osmiridium ( an alloy of osmium and iridium ) . in chemical compounds it is mainly in an oxygenation state of iv ; oxygenation states ii , iii , and vi are also possible , and it has good properties of electric and thermal conductivity . discovered in 1803 by smithson tennant iridium was named after the greek rainbow goddess iris because of its different coloured salts . annual production of iridium is only 3 tonnes ; it is one of the rarest elements in nature . at , iridium has been used together with platinum as a component of electrodes for stimulation . iridium oxide was used instead of ag / agcl in dry electrodes with microtips that could be used without gel eeg . because of the high price of iridium there was an attempt to produce electrodes with titanium - iridium oxide . in oncology iridium has found its way as ir isotope in brachytherapy . they can be used in after - loading systems that protect medical staff from radiation . it is one of the basic isotopes used in brachytherapy . in the field of gynaecological oncology it is used mainly in plesiobrachytheraphy in cervical and uterine cancer [ 48 , 49 ] . research was made on the use of iridium in flt4 ( also known as vegfr3 ) kinase inhibitor [ 50 , 51 ] . ruthenium ( ru ) , with atomic number 44 , atomic mass 101.07 , density 12.45 g / cm , and melting point 2334c , is found in nature as sulphide , iron , and chrome ores . in chemical compounds some researchers claim that ruthenium was first discovered in 1808 by jdrzej niadecki ; he called this element vestium in honour of the discovery of the planet vesta . the first ruthenium compound used in clinical practice was nami - a . a is used together with gemcitabine as second - line chemotherapy in the treatment of metastases in non - small cell lung carcinoma . other compounds used in clinical practice are kp1019 , and soluble salt kp1339 , which has finished phase i of a clinical trial in neuroendocrine carcinomas . electroporation of kp1339 was tested in slovenia , and this method was found to be effective in vivo because of its extra antiangiogenic properties . it may also spread the idea of electrochemotherapy , which is based on local injection of chemotherapeutics accompanied by electrical impulses . developed dohuru , hothyru , and tothyru , which are aziru derivatives , and together with phospholipids they created stable nanoaggregates . the antiproliferative activity of nanocompounds towards cell lines widr , c6 , and mcf-7 was also studied .
worldwide research groups are searching for anticancer compounds , many of them are organometalic complexes having platinum group metals as their active centers . most commonly used cytostatics from this group are cisplatin , carboplatin and oxaliplatin . 
 cisplatin was used fot the first time in 1978 , from this time many platinum derivatives were created . in this review 
 we present biological properties and probable future clinical use of platinum , gold , silver , iridium and ruthenium derivatives . 
 gold derivative auranofin has been studied extensively . 
 action of silver nanoparticles on different cell lines was analysed . 
 iridium isotopes are commonly used in brachyterapy . 
 ruthenium compound new anti - tumour metastasis inhibitor ( nami - a ) is used in managing lung cancer metastases . 
 electroporation of another ruthenium based compound kp1339 was also studied . 
 most of described complexes have antiproliferative and proapoptotic properties . 
 further studies need to be made . 
 nevertheless noble metal based chemotherapheutics and compounds seem to be an interesting direction of research .