Result
| Gene | Variant | Type | Tumor | Drug | Drug level | Reference | More | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AR | AMP | CNA | Prostate Cancer | AR inhibitor next gens | V | 2 | |||||||
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Evidence region
CGI Patient Criteria- NoteEnzalutamide has demonstrated impressive efficacy in men with metastatic CRPC, moving swiftly from a phase I/II study to two pivotal phase III trials testing this agent in both chemotherapy-pretreated as well as chemotherapy-naive CRPC patients. Ongoing studies are aiming to explore the utility of enzalutamide in earlier stages of the disease, and to investigate the optimal sequencing and combination of enzalutamide with other standard and novel therapies for prostate cancer. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Sorry, there is no related drug information. |
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| AR | AMP | CNA | Prostate Cancer | Abiraterone | RII | 1 | |||||||
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Evidence region
CGI Patient Criteria- NotePatients with AR gain or T878A or L702H pre-abiraterone (45%) were 4.9 times and 7.8 times less likely to have a decline in PSA by >=0% or >=0% respectively and had a significantly worse overall (HR 7.33, 95% CI 3.51-15.34) and progression-free (HR 3.73, 95% CI 2.17-6.41) survival. Evaluation of plasma AR using next-generation sequencing could identify cancers with primary resistance to abiraterone. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Abiraterone DrugBank ID Synonyms(3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-ol Zytiga Abiraterone is a derivative of steroidal progesterone and is an innovative drug that offers clinical benefit to patients with hormone refractory prostate cancer. Abiraterone is administered as an acetate salt prodrug because it has a higher bioavailability and less susceptible to hydrolysis than abiraterone itself. FDA approved on April 28, 2011. Target gene
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| AR | F877L | MUT | Prostate Cancer | Apalutamide | RII | 1 | |||||||
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Evidence region
CGI Patient Criteria- NoteA missense mutation in the ligand-binding domain of the androgen receptor F876L confers resistance to the second-generation antiandrogens enzalutamide and ARN-509 in preclinical models of AR function and prostate cancer and is detected in plasma DNA from ARN-509-treated patients with progressive disease. These results chart a new path for the discovery and development of next-generation antiandrogens that could be coupled with a blood-based companion diagnostic to guide treatment decisions. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Apalutamide DrugBank ID SynonymsApalutamide BrandErleada DescriptionApalutamide 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 [A31846]. 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 [A31846]. In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of [DB01128] or [DB08899]. Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines [A31846]. 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 [A31852]. 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 [L1295]. Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death [A31846]. 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 [A31846]. 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 [L1295]. 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 [L1295]. Target gene
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| AR | F877L | MUT | Prostate Cancer | Enzalutamide | RII | 1 | |||||||
|
Evidence region
CGI Patient Criteria- NoteA missense mutation in the ligand-binding domain of the androgen receptor F876L confers resistance to the second-generation antiandrogens enzalutamide and ARN-509 in preclinical models of AR function and prostate cancer and is detected in plasma DNA from ARN-509-treated patients with progressive disease. These results chart a new path for the discovery and development of next-generation antiandrogens that could be coupled with a blood-based companion diagnostic to guide treatment decisions. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Enzalutamide DrugBank ID SynonymsEnzalutamida Xtandi DescriptionEnzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012. Target gene
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| AR | F877L | MUT | Prostate Cancer | Enzalutamide | V | 1 | |||||||
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Evidence region
CGI Patient CriteriaAR (T878A) NoteMolecular modeling revealed favorable structural changes in the double-mutant AR that lead to a decrease in steric clashes for enzalutamide. Ligand-binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for enzalutamide, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in coregulator recruitment and chromatin interactions. Our data show that enzalutamide is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double-mutant AR. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Enzalutamide DrugBank ID SynonymsEnzalutamida Xtandi DescriptionEnzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012. Target gene
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| AR | F877L | MUT | Prostate Cancer | Apalutamide | RIII | 1 | |||||||
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Evidence region
CIVIC Patient Criteria- NoteMutations F876L in the ligand binding domain of the androgen receptor confered resistance to enzalutamide and ARN-509, causing these compounds to function as partial agonists in two prostate cancer cell lines. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Apalutamide DrugBank ID SynonymsApalutamide BrandErleada DescriptionApalutamide 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 [A31846]. 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 [A31846]. In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of [DB01128] or [DB08899]. Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines [A31846]. 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 [A31852]. 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 [L1295]. Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death [A31846]. 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 [A31846]. 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 [L1295]. 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 [L1295]. Target gene
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| AR | F877L | MUT | Prostate Cancer | Enzalutamide | RIII | 1 | |||||||
|
Evidence region
CIVIC Patient Criteria- NoteMutations F876L in the ligand binding domain of the androgen receptor confered resistance to enzalutamide and ARN-509, causing these compounds to function as partial agonists in two prostate cancer cell lines. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Enzalutamide DrugBank ID SynonymsEnzalutamida Xtandi DescriptionEnzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012. Target gene
|
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| AR | L702H | MUT | Prostate Cancer | Abiraterone | RII | 1 | |||||||
|
Evidence region
CGI Patient Criteria- NotePatients with AR gain or T878A or L702H pre-abiraterone (45%) were 4.9 times and 7.8 times less likely to have a decline in PSA by >=0% or >=0% respectively and had a significantly worse overall (HR 7.33, 95% CI 3.51-15.34) and progression-free (HR 3.73, 95% CI 2.17-6.41) survival. Evaluation of plasma AR using next-generation sequencing could identify cancers with primary resistance to abiraterone. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Abiraterone DrugBank ID Synonyms(3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-ol Zytiga Abiraterone is a derivative of steroidal progesterone and is an innovative drug that offers clinical benefit to patients with hormone refractory prostate cancer. Abiraterone is administered as an acetate salt prodrug because it has a higher bioavailability and less susceptible to hydrolysis than abiraterone itself. FDA approved on April 28, 2011. Target gene
|
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| AR | Oncogenic Mutations | MUT | Prostate Cancer | Bicalutamide | RII | 1 | |||||||
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Evidence region
CIVIC Patient Criteria- NoteIn a study of 150 patients with metastatic castration resistant prostate cancer (mCRPC), 71.3% of cases (n=107) harbored androgen receptor (AR) pathway aberrations. Within the AR mutation cohort, 78 patients had AR amplification mutations, 16 patients had AR missense mutations, and 13 patients had mutations in ZBTB16, NCOR1, FOXA1, and SPOP, which are all AR regulators or downstream effectors. All AR mutations were exclusive to mCRPC neoplasms and were not found in primary prostate cancer. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Bicalutamide DrugBank ID SynonymsBicalutamida Jamp-bicalutamide Bicalutamide is an oral non-steroidal anti-androgen for prostate cancer. It is comprised of a racemic mixture that is a 50:50 composition of the (R)-bicalutamide and (S)-bicalutamide enantionmers. Bicalutamide binds to the androgen receptor. Target gene
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| AR | Oncogenic Mutations | MUT | Prostate Cancer | Cyproterone acetate | RII | 1 | |||||||
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Evidence region
CIVIC Patient Criteria- NoteIn a study of 150 patients with metastatic castration resistant prostate cancer (mCRPC), 71.3% of cases (n=107) harbored androgen receptor (AR) pathway aberrations. Within the AR mutation cohort, 78 patients had AR amplification mutations, 16 patients had AR missense mutations, and 13 patients had mutations in ZBTB16, NCOR1, FOXA1, and SPOP, which are all AR regulators or downstream effectors. All AR mutations were exclusive to mCRPC neoplasms and were not found in primary prostate cancer. Gene name
Full name
androgen receptor Gene typeprotein-coding FunctionThe androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017] Drug name
Cyproterone acetate DrugBank ID SynonymsCyproterone 17-O-acetate Cléo -35 An anti-androgen that, in the form of its acetate (cyproterone acetate), also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. Target gene
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