You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
ovarian cancer is called  the silent killer  because of its not - so - obvious symptoms such as fatigue , weight change , abdominal distention and pain .
the lack of efficient and early detection is the reason for the high mortality rate .
the  gold standard  of ovarian cancer treatment consists of surgery followed by carboplatin alone , or a combination of chemotherapy with carboplatin and paclitaxel ( ptx ) .
currently , first line therapy in early disease ( stages i  iia ) is only surgery . in 25% of patients ,
this protocol does not cure , and the disease will recur . in advanced stages ( iia 
iv ) , the current standard of care is cytoreduction followed by platinum - based chemotherapy .
the most common adverse effects include haematological disorders , nausea , vomiting , disruption of the bone cycle and pain . according to most patients , alopecia is one of the most distressing side effects .
drugs commonly used in ovarian cancer treatment ( paclitaxel , docetaxel ) cause severe alopecia which markedly lowers the quality of patients lives [ 5 , 6 ] .
there is a need to investigate and find new drugs which will selectively and effectively treat ovarian cancer , and also be able to overcome multidrug resistance ( mdr )  the factor responsible for many cases of recurrent epithelial ovarian cancer ( eoc ) .
trabectedin , also known as yondelis or et-743 , is an anti - tumour drug , originally derived from the marine tunicate ecteinascidia turbinata .
1 ) . two of the rings covalently bind the n2 amino group in the guanine residue in the dna minor groove , in contrast to traditional alkylating drugs that bind guanine at the n7 or o6 position in the dna major groove .
the adducts are stabilized by van der waals interactions and hydrogen bonds between rings a and b and dna [ 7 , 8 ] .
trabectedin induces dna alkylation and dna - protein crosslinks which cause formation of dna strand breaks [ 7 , 9 , 10 ] .
trabectedin causes disruption of transcription by inhibition of the transcription - dependent nucleotide excision repair system ( ner ) , followed by g2/m arrest and activation of the extrinsic and intrinsic apoptotic pathways , occurring through p53-independent process [ 7 , 11 , 12 ]
. data on hela , chinese hamster and human leukaemia cells obtained by soares et al
.   indicated that dna synthesis and cellular viability were reduced by 50% after 1 h exposure to , respectively , 30 nm and 20 nm trabectedin .
it was associated with formation of difficult - to - repair drug - dna adducts , converted later into dna double - strand breaks ( dsbs ) .
furthermore , trabectedin toxicity was 8-fold higher toward brca2 deficient cells compared with the parental cell lines .
unrepaired dsbs in brca2-deficient cells led to chromosomal aberrations . due to the promising outcomes of trabectedin ,
trabectedin was approved in the european union in july 2007 for the treatment of soft - tissue sarcomas ( sts ) in adults after failure of conventional therapy including anthracyclines and ifosfamide [ 7 , 9 , 11 ] . in a preclinical study , it demonstrated antineoplastic activity in vitro and in vivo in ovarian , breast , prostate , renal , melanoma and non - small cell lung cancer .
it is effective in ovarian carcinoma xenografts and ovarian cancer explants and can be combined with cisplatin .
unfortunately , in vitro studies with mammalian cells transfected with mdr1 genes and an in vivo study in mice with p - gp overexpression showed that trabectedin is a substrate of p - glycoprotein ( p - gp ) , the molecule responsible for multidrug resistance in human cancer cells .
anti - tumour activity of trabectedin in ovarian cancer has been studied in phase i and phase ii clinical trials . the phase i trial study included women with platinum - sensitive and platinum - resistant ovarian cancer after therapy based on platinum and taxanes .
trabectedin caused 43% response rates in patients with platinum - sensitive ovarian cancer , with a time to progression of 7 to 9 months .
there were also observed two partial responses among women with platinum - resistant ovarian cancer .
the most common adverse effects were nausea and vomiting ( 78% ) , neutropenia ( 41% ) , asthenia ( 78% ) and thrombocytopenia ( 7.5% ) .
phase ii clinical trials included women with recurrent ovarian cancer after one or two platinum - based chemotherapy regimens .
trabectedin showed 29% and 6.3% response rates in women with platinum - sensitive and platinum - resistant ovarian cancer respectively , with a median progression time of between 5.1 and 2 months .
the side effects were neutropenia ( 8% ) , nausea , vomiting , and fatigue ( 5% ) .
anti - tumour effectiveness of trabectedin in monotherapy was evaluated by mabuchi et al . 
 in vitro using 3 lines of human ovarian clear cell carcinoma ( ccc ) and human ovarian serous adenocarcinomas ( sac )  3 lines .
then , the anti - tumour effect of trabectedin was evaluated in vivo using a xenograft model with mice inoculated with ccc cells .
after 4 weeks of treatment the tumour mass was reduced by greater than 70% , compared with pbs - treated mice .
it is metabolized in the liver with a half - life of approximately 90 hours .
the major tissue toxicities are connected with the bile duct ( elevated plasma bilirubin , bile acids and aspartate transaminase ( ast ) , alanine transaminase ( alt ) , -glutamyl transferase ( ggt ) and alkaline phosphatase activities ) .
the most common side effects are fatigue , nausea , anorexia , vomiting , constipation , atelectasis , dyspnoea , neutropenia , haemorrhoids , and intestinal obstruction .
there were no indications of renal toxicity in rats ( or mice and dogs ) [ 7 , 14 , 17 , 18 ] .
there is also no cardiac toxicity and no ecg changes ( considered as prolongation of qt / qtc interval ) after treatment with trabectedin .
very interesting data were obtained for the combination of trabectedin with pegylated liposomal doxorubicin ( pld , doxil ) .
this modification prevents plasma protein adsorption to the liposome surface and showed that in contrast to non - pegylated liposomes , plds are able to remain in the circulation much longer . due to the enhanced permeability and retention ( epr ) effect
, the liposomes delivered drugs more specifically to the cancer tissues and limited exposure of normal cells to the drugs .
the use of pld for ovarian cancer treatment gave promising results [ 19 , 20 ] .
based on the results of a randomized phase iii trial ( et-743-ova-301 ) ( comparing pld alone with a combination of pld and trabectedin ) , on 672 patients diagnosed with a recurrent ovarian cancer from 21 countries in 2009 , the european commission approved the combination with pld : 30 mg / m ( as a 3 h infusion ) , every 3 weeks , for the treatment of patients with a recurrent platinum - sensitive ovarian cancer , for whom a first line platinum - based chemotherapy had failed [ 14 , 21 , 22 ] .
the study demonstrated that trabectedin in combination with pld improves progression - free survival ( pfs ) and overall response rate ( orr ) in comparison to doxil alone as a second - line treatment of recurrent ovarian cancer . among the 672 patients , 522 ( 77.7% ) deaths
were observed ( including 258 in the trabectedin and doxil arm and 264 in the doxil arm ) . the median overall survival ( os ) for trabectedin plus doxil and
surprisingly , the progression - free interval ( pfi ) favouring the pld arm ( pld  pfi ) was 13.3 months , whereas trabectedin + pld  pfi was 10.6 months . additionally , this combination was well tolerated , with manageable toxicity .
furthermore , a decrease of pld - associated toxicity was observed , which supports the thesis that trabectedin in combination with pld is a good solution for patients with recurrent ovarian cancers [ 2123 ] .
angiogenesis  the creation of new blood and lymphatic vessels  is a crucial process for tumour development .
most types of tumours respond to a hypoxic environment by secreting a key pro - angiogenic growth factor called vascular endothelial growth factor ( vegf ) .
these particles bind to its receptors ( vegfr-1 , vegfr-2 , vegfr-3 ) on the surface of cancer cells , leading to metastasis
.   showed that the overexpression of vegfr-2 occurred among patients with early ovarian cancer stages ( figo  i , iia ) , which may indicate the important role of apoptosis during this phase , whereas an increased level of vegfr-3 was detected in advanced stages of cancer , and correlated with a positive response to chemotherapy .
a high level of vegfr-3 is also connected with aggressiveness of ovarian cancer and indicates poor prognosis .
vasculogenic mimicry is a phenomenon connected with the formation of fluid - conducting channels , not lined with endothelium .
this process occurs during tumour development and concerns undifferentiated cancers especially in the advanced stage of the disease .
additionally , some researchers claim that vasculogenic mimicry may protect the neoplasm against anticancer agents ( as tumours demonstrating this phenomenon are often drug - resistant ) .
currently the most studied agent among anti - angiogenic drugs is bevacizumab  a humanized igg1 monoclonal antibody which selectively inhibits vegf activity .
two phase iii clinical trials , gog-218 and icon7 , showed a significant benefit in pfs when the standard ( carboplatin - paclitaxel ) chemotherapy was combined with bevacizumab . based on these results , the european medicines agency ( ema ) approved this combination of drugs for the front line treatment of advanced epithelial ovarian cancer .
.   indicated that bevacizumab in combination with trabectedin and oxaliplatin causes complete remission of recurrent ovarian clear cell carcinoma , with manageable general toxicity .
it is thought that bevacizumab blocks vascular repair and survival , which enhances the activity of trabectedin and oxaliplatin .
the latest studies indicate that angiogenesis and vasculogenic mimicry are important in tumour development ; therefore deeper understanding of the individual angiogenic patient 's phenotype may be helpful in designing an appropriate and effective anticancer therapy .
over 225 000 new cases of ovarian cancer are diagnosed each year . 
 symptoms are often vague , so most cases are detected when the disease is at an advanced stage . 
 there is a need to find new drugs which will be able to treat ovarian cancer effectively . 
 one of the most promising antineoplastic agents is trabectedin ( yondelis ) , derived from the marine tunicate ecteinascidia turbinata , approved by the european union in july 2007 for the treatment of soft - tissue sarcomas . 
 this drug shows a mechanism of action based on the inhibition of the nucleotide excision repair system . 
 trabectedin shows anti - tumour activity in vitro and in vivo in ovarian , breast , prostate , renal , melanoma and non - small cell lung cancer cell lines . 
 trabectedin in combination with pegylated liposomal doxorubicin demonstrates synergistic antineoplastic activity .