先進的な前立腺がんの治療のための第2世代の抗アンドロゲンの開発
Chris Tran1, Samedy Ouk, Nicola J Clegg
1Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Science (New York, N.Y.)
|April 11, 2009
まとめ
新しい抗アンドロゲン化合物であるRD162とMDV3100は,進行した前立腺がんを効果的に治療します. 彼らは,アンドロゲン受容体の活性を抑制することによって,カストレーションに抵抗する前立腺がんを標的とし,臨床前および早期臨床研究で有望な結果を示しています.
科学分野:
- 腫瘍学 腫瘍学
- 薬理学 薬理学とは
- 分子生物学は分子生物学である.
背景:
- 転移性前立腺がんの治療は,耐性メカニズムのためにしばしば失敗します.
- カストレーション耐性前立腺がん (CRPC) は,アンドロゲン受容体 (AR) 発現が上昇した結果に起因する.
- 既存の抗アンドロゲン療法がCRPCに対して無効になる.
研究 の 目的:
- 新しい非ステロイド性アンチアンドロゲン,RD162とMDV3100を特徴付ける.
- CRPCの臨床前モデルの有効性を評価する.
- 臨床試験の第I・第II相において,その安全性と初期有効性を評価する.
主な方法:
- RD162およびMDV3100の化合物は,非ステロイド抗アンドロゲンのスクリーンから最適化されました.
- AR結合親和性,核転位,DNA結合,およびコアクティベーターの採用が評価されました.
- In vivoの有効性は,CRPCのマウスモデルでテストされました.
- 進行性前立腺がん患者のMDV3100を評価するために,第I/II相臨床試験が行われました.
主要な成果:
- RD162とMDV3100は,ビカルウタミドよりも高いAR結合親和性を示した.
- この2つの化合物は,AR核転位,DNA結合,およびコアクティベーター募集を阻害した.
- RD162とMDV3100は,CRPCマウスモデルにおける腫瘍回帰を誘導した.
- 臨床試験では,MDV3100で治療を受けた患者の43%が前立腺特異抗原 (PSA) の有意な減少を示した.
結論:
- RD162とMDV3100は,CRPCに対して有効な強力な非ステロイド抗アンドロゲンです.
- これらの化合物は,進行した前立腺がんの有望な治療候補である.
- MDV3100は,CRPC治療のためのより大きな臨床試験でさらなる調査を正当化しています.
関連する概念動画
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:56Treatment Resistent Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...