DDInter1840 DDInter107
Trabectedin, also referred as ET-743 during its development, is a marine-derived antitumor agent discovered in the Carribean tunicate _Ecteinascidia turbinata_ and now produced synthetically. Trabectedin has a unique mechanism of action. It binds to the minor groove of DNA interfering with cell division and genetic transcription processes and DNA repair machinery. It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is currently under evaluation for the treatment of breast cancer, prostate cancer, in addition to pediatric sarcomas. Both the European Commission and the U.S. Food and Drug Administration (FDA) have approved trabectedin as an orphan drug in soft tissue sarcomas and ovarian cancer. On October 23, 2015, the FDA approved trabectedin, (as Yondelis), for the treatment of specific soft tissue sarcomas.
Apalutamide is a potent androgen receptor (AR) antagonist that selectively binds to the ligand-binding domain of AR and blocks AR nuclear translocation or binding to androgen response elements . It has been used in trials studying the treatment of Prostate Cancer, Hepatic Impairment, Prostatic Neoplasms, Castration-Resistant Prostate Cancer, and Prostatic Neoplasms, Castration-Resistant, among others. Exerting an antitumor action, apalutamide blocking the effect of androgens that promote tumor growth. It targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets in prostate tumors . In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of or . Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines . Androgen-deprivation therapy, or hormone therapy, can be used as part of maintenance therapy for patients with non-metastatic prostate cancer. Although most patients achieve therapeutic responses at the initial hormone therapy, many patients progress to non-metastatic castration-resistant (resistance to hormone therapy) prostate cancer which is the second-most common cause of cancer-related deaths in American males . Castration-resistant prostate cancer is often incurable, which poses significant clinical challenges for patients. Approximately 10 to 20 % of prostate cancer cases are castration-resistant, and up to 16% of these patients show no evidence of cancer metastasis at the time of castration-resistant diagnosis . Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death . In a phase-2 multicenter open-label study, 89% of patients with non-metastatic, castration-resistant prostate cancer had ≥50% PSA decline at week 12 of apalutamide treatment . In a randomized trial, the median metastasis-free survival for patients taking apalutamide was 40.5 months compared to 16.2 months for patients taking a placebo . Apalutamide displayed good tolerability and safety profile in clinical studies. Apalutamide was approved in February 2018 by the FDA as Erleada for the treatment of patients with non-metastatic prostate cancer that is resistant to treatment with hormone therapy (castration-resistant). It is available as oral tablets. Apalutamide is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer .
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is bound by {v} (Compound) Dasatinib
Dasatinib {u} may lead to a major life threatening interaction when taken with {v} Apalutamide
Trabectedin {u} (Compound) binds {v} (Gene) PTGS1
PTGS1 {u} (Gene) is bound by {v} (Compound) Ketoprofen
Ketoprofen {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Pentamidine
Pentamidine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
Trabectedin {u} (Compound) binds {v} (Gene) PTGS1
PTGS1 {u} (Gene) is bound by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Apalutamide
Trabectedin {u} (Compound) is included by {v} (Pharmacologic Class) Alkylating Activity
Alkylating Activity {u} (Pharmacologic Class) includes {v} (Compound) Ifosfamide
Ifosfamide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
Trabectedin {u} (Compound) causes {v} (Side Effect) Alanine aminotransferase increased
Alanine aminotransferase increased {u} (Side Effect) is caused by {v} (Compound) Trametinib
Trametinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
Trabectedin {u} (Compound) causes {v} (Side Effect) Alanine aminotransferase increased
Alanine aminotransferase increased {u} (Side Effect) is caused by {v} (Compound) Eplerenone
Eplerenone {u} may cause a minor interaction that can limit clinical effects when taken with {v} Apalutamide
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is bound by {v} (Compound) and {u} (Gene) is upregulated by {v} (Compound) Crizotinib
Crizotinib {u} may lead to a major life threatening interaction when taken with {v} Apalutamide
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Toremifene
Toremifene {u} may lead to a major life threatening interaction when taken with {v} Apalutamide
Trabectedin {u} (Compound) causes {v} (Side Effect) Vomiting
Vomiting {u} (Side Effect) is caused by {v} (Compound) Procainamide
Procainamide {u} may lead to a major life threatening interaction when taken with {v} Apalutamide
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Dasatinib (Compound) and Dasatinib may lead to a major life threatening interaction when taken with Apalutamide
Trabectedin (Compound) binds PTGS1 (Gene) and PTGS1 (Gene) is bound by Ketoprofen (Compound) and Ketoprofen may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Pentamidine (Compound) and Pentamidine may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
Trabectedin (Compound) binds PTGS1 (Gene) and PTGS1 (Gene) is bound by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Apalutamide
Trabectedin (Compound) is included by Alkylating Activity (Pharmacologic Class) and Alkylating Activity (Pharmacologic Class) includes Ifosfamide (Compound) and Ifosfamide may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
Trabectedin (Compound) causes Alanine aminotransferase increased (Side Effect) and Alanine aminotransferase increased (Side Effect) is caused by Trametinib (Compound) and Trametinib may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
Trabectedin (Compound) causes Alanine aminotransferase increased (Side Effect) and Alanine aminotransferase increased (Side Effect) is caused by Eplerenone (Compound) and Eplerenone may cause a minor interaction that can limit clinical effects when taken with Apalutamide
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Crizotinib (Compound) and SRC (Gene) is upregulated by Crizotinib (Compound) and Crizotinib may lead to a major life threatening interaction when taken with Apalutamide
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Toremifene (Compound) and Toremifene may lead to a major life threatening interaction when taken with Apalutamide
Trabectedin (Compound) causes Vomiting (Side Effect) and Vomiting (Side Effect) is caused by Procainamide (Compound) and Procainamide may lead to a major life threatening interaction when taken with Apalutamide