Advanced Ovarian Cancer

Also known as: Advanced Ovarian cancer / Ovarian Cancer Stage IV / Ovarian epithelial cancer metastatic / Ovarian epithelial cancer stage IV / Ovarian cancer metastatic

DrugDrug NameDrug Description
DB00441GemcitabineGemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide"). Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.
DB00526OxaliplatinOxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as Folfox for the treatment of colorectal cancer. Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility. Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.
DB01229PaclitaxelPaclitaxel is a chemotherapeutic agent marketed under the brand name Taxol among others. Used as a treatment for various cancers, paclitaxel is a mitotic inhibitor that was first isolated in 1971 from the bark of the Pacific yew tree which contains endophytic fungi that synthesize paclitaxel. It is available as an intravenous solution for injection and the newer formulation contains albumin-bound paclitaxel marketed under the brand name Abraxane.
DB12332RucaparibRucaparib is a potent mammalian poly(ADP-ribose) polymerase (PARP) 1, 2 and 3 inhibitor with anticancer properties. PPAR is an enzyme that plays an essential role in DNA repair by activating response pathways and facilitating repair [A18745], and defects in these repair mechanisms have been demonstrated in various malignancies, including cancer. Regulation of repair pathways is critical in promoting necessary cell death. BRCA genes are tumor suppressor genes mediate several cellular process including DNA replication, transcription regulation, cell cycle checkpoints, apoptosis, chromatin structuring and homologous recombination (HR). Homologous recombination deficiency (HRD), along with PPAR inhibition, is a vulnerability that enhances the cell death pathway when the single mutations alone would permit viability. Ovarian cancer commonly possesses defects in DNA repair pathways such as HRD due to BRCA mutations or otherwise. There are three main types of ovarian cancer: epithelial (90%), germ cell (5%) and sex cord stromal cell (5%). Epithelial ovarian, being the most common, fifth leading cause of cancer-related deaths in women in the United States. Advanced ovarian cancer particularly poses challenges due to reduced therapeutic response rates from standard platinum-based chemotherapy and overall survival rates. Rucaparib has shown to induce cytotoxicity in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes [FDA Label]. Of all the BRCA1/2 mutations in ovarian cancer, most are due to germline mutations (18%), and approximately 7% represent somatic mutations acquired within the tumor [A31354]. The indication of rucaparib as an oral monotherapy in patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer was granted accelerated approval in 2016 for selected patients who have previously received greater than two lines of platinum-based therapy. It is currently marketed in the US under the brand name Rubraca that contains rucaparib camsylate as the active ingredient. The identification of patients who are eligible for rucaparib therapy is performed via *in vitro* diagnostic tests to detect the presence of a deleterious BRCA mutation (germline and/or somatic). The FDA-approved test qualitatively detects sequence alterations in BRCA1 and BRCA2 (BRCA1/2) genes. More information can be found on the FDA Website [L1047]. While rucaparib is indicated for deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer, there is evidence that its antitumor activity is also clinically effective against ovarian tumors with high homologous recombination deficiency (HRD) loss of heterozygosity (LOH) [A31354].
DrugDrug NameTargetType
DB00441GemcitabineRibonucleoside-diphosphate reductase large subunittarget
DB00441GemcitabineUMP-CMP kinasetarget
DB00441GemcitabineThymidylate synthasetarget
DB00441GemcitabineCytidine deaminaseenzyme
DB00441GemcitabineDeoxycytidine kinaseenzyme
DB00441GemcitabineMultidrug resistance protein 1transporter
DB00441GemcitabineMultidrug resistance-associated protein 7transporter
DB00441GemcitabineEquilibrative nucleoside transporter 1transporter
DB00441GemcitabineSodium/nucleoside cotransporter 1transporter
DB00441GemcitabineEquilibrative nucleoside transporter 2transporter
DB00441GemcitabineSolute carrier family 28 member 3transporter
DB00526OxaliplatinSolute carrier family 22 member 2transporter
DB00526OxaliplatinHigh affinity copper uptake protein 1transporter
DB00526OxaliplatinSolute carrier family 22 member 3transporter
DB00526OxaliplatinATP-binding cassette sub-family G member 2transporter
DB00526OxaliplatinCytochrome P450 1A1enzyme
DB00526OxaliplatinCytochrome P450 1B1enzyme
DB00526OxaliplatinCytochrome P450 2E1enzyme
DB00526OxaliplatinGlutathione S-transferase theta-1enzyme
DB00526OxaliplatinSuperoxide dismutase [Cu-Zn]enzyme
DB00526OxaliplatinGlutathione S-transferase Penzyme
DB00526OxaliplatinGlutathione S-transferase Mu 1enzyme
DB00526OxaliplatinNAD(P)H dehydrogenase [quinone] 1enzyme
DB00526OxaliplatinCanalicular multispecific organic anion transporter 1transporter
DB00526OxaliplatinCopper-transporting ATPase 2transporter
DB00526OxaliplatinCopper-transporting ATPase 1transporter
DB01229PaclitaxelApoptosis regulator Bcl-2target
DB01229PaclitaxelTubulin beta-1 chaintarget
DB01229PaclitaxelCytochrome P450 2C8enzyme
DB01229PaclitaxelCytochrome P450 3A4enzyme
DB01229PaclitaxelCytochrome P450 3A5enzyme
DB01229PaclitaxelCytochrome P450 3A7enzyme
DB01229PaclitaxelBile salt export pumptransporter
DB01229PaclitaxelMultidrug resistance protein 1transporter
DB01229PaclitaxelMultidrug resistance-associated protein 1transporter
DB01229PaclitaxelMultidrug resistance-associated protein 7transporter
DB01229PaclitaxelCytochrome P450 19A1enzyme
DB01229PaclitaxelCytochrome P450 1B1enzyme
DB01229PaclitaxelSolute carrier organic anion transporter family member 1B3transporter
DB01229PaclitaxelNuclear receptor subfamily 1 group I member 2target
DB01229PaclitaxelMicrotubule-associated protein 4target
DB01229PaclitaxelMicrotubule-associated protein 2target
DB01229PaclitaxelMicrotubule-associated protein tautarget
DB01229PaclitaxelATP-binding cassette sub-family G member 2transporter
DB01229PaclitaxelCanalicular multispecific organic anion transporter 1transporter
DB12332RucaparibPoly [ADP-ribose] polymerase 1target
DB12332RucaparibPoly [ADP-ribose] polymerase 2target
DB12332RucaparibPoly [ADP-ribose] polymerase 3target
DB12332RucaparibCytochrome P450 2D6enzyme
DB12332RucaparibCytochrome P450 1A2enzyme
DB12332RucaparibCytochrome P450 3A4enzyme
DB12332RucaparibMultidrug resistance protein 1transporter
DB12332RucaparibATP-binding cassette sub-family G member 2transporter
DB12332RucaparibMultidrug and toxin extrusion protein 1transporter
DB12332RucaparibMultidrug and toxin extrusion protein 2transporter
DB12332RucaparibSolute carrier family 22 member 1transporter
DB12332RucaparibMultidrug resistance-associated protein 4transporter
DB12332RucaparibSolute carrier organic anion transporter family member 1B1transporter
DB12332RucaparibSolute carrier organic anion transporter family member 1B3transporter
DB12332RucaparibSolute carrier family 22 member 6transporter
DB12332RucaparibSolute carrier family 22 member 8transporter
DB12332RucaparibCytochrome P450 3A5enzyme
DB12332RucaparibCytochrome P450 3A7enzyme
DB12332RucaparibCytochrome P450 3A43enzyme
DB12332RucaparibCytochrome P450 2C19enzyme
DB12332RucaparibCytochrome P450 2C9enzyme
DB12332RucaparibCytochrome P450 2C8enzyme
DB12332RucaparibUDP-glucuronosyltransferase 1-1enzyme
DrugDrug NamePhaseStatusCount
DB00958Carboplatin1Active Not Recruiting1
DB14865Human interleukin-21Recruiting1
DB09074Olaparib1Active Not Recruiting1
DB04964Oregovomab1Active Not Recruiting1
DB01229Paclitaxel1Active Not Recruiting1
DB00958Carboplatin1 / 2Recruiting1
DB01229Paclitaxel1 / 2Recruiting1
DB09037Pembrolizumab1 / 2Recruiting1
DB11760Talazoparib1 / 2Recruiting1
DB00112Bevacizumab2Not Yet Recruiting1
DB09037Pembrolizumab2Not Yet Recruiting1
DB00958Carboplatin3Not Yet Recruiting1
DB09074Olaparib3Active Not Recruiting1
DB01229Paclitaxel3Not Yet Recruiting1