薬剤トリオががん治療の有効性を改善し心臓を保護した（Abstract # 16494）

シルデナフィルとrapamycinは相互に作用しドキソルビシンのがん治療を改善し心臓を保護する

Sildenafil and rapamycin work together to improve doxorubicin cancer treatment while protecting the heart

がん治療薬ドキソルビシンと勃起不全改善薬シルデナフィルおよび免疫抑制剤rapamycinの併用はがん細胞死滅に役立ち心臓を傷害から保護したとのスタディ結果が、2012年American Heart Association学会で発表された。この数十年の間ドキソルビシンは、乳がん、卵巣がん、結腸および前立腺がんなどの種々の人間のがんに対する強力な抗がん剤である。しかし、この薬剤は心臓に対し不可逆な影響を与える可能性がありその毒性のために使用が制限されている。このスタディでは、細胞および動物モデルを使用し、シルデナフィル単独またはrapamycinとの併用はドキソルビシンの抗がん作用を有意に改善し心臓を保護することを示した。この薬剤併用は心筋をアポトーシスから劇的に保護し、壊死の範囲を減少させた。この3剤全ての併用は最も強力な効果を示した。この薬剤併用はがん患者の余命を改善する可能性があると研究者らは確信している。さらに研究を行い、シルデナフィルやrapamycinがどのように相互に作用しドキソルビシン治療を改善するのかを理解する必要がある。

Combining the cancer medication doxorubicin with sildenafil, a drug for erectile dysfunction, and rapamycin, an immunosuppressant, helped kill cancer cells and protected the heart from damage, in a study presented at the American Heart Association's Scientific Sessions 2012.

For decades, doxorubicin has been a powerful anti-cancer treatment for various human cancers, including breast, ovarian, colon and prostate. But its use has been limited due to harmful, possibly irreversible effects on the heart.

In this study, using cell and animal models, researchers found that sildenafil alone or in combination with rapamycin (an immunosuppressant used to prevent post-transplant organ rejection) significantly improved the anti-cancer effects of doxorubicin while protecting the heart. The combination of all three medications showed the most powerful effect, researchers said.

"Because sildenafil and rapamycin are clinically approved drugs that both protect heart muscle, we thought that combining these drugs with doxorubicin would be a unique strategy to eliminate the cardiac side effects of doxorubicin while further improving its cancer-killing ability," said Rakesh Kukreja, Ph.D., study co-author and professor of internal medicine and cardiology, Virginia Commonwealth University (VCU) School of Medicine in Richmond.

"The drug combination led to a dramatic protection of heart muscle from apoptosis and, to a lesser extent, necrosis," said David E. Durrant, study lead author and Ph.D. candidate at the VCU School of Medicine. "We think this combination therapy may have excellent potential to move forward into clinical trials and eventually improve life expectancy of cancer patients."

More research is needed to understand how sildenafil and rapamycin work together to improve doxorubicin treatment, Durrant said.

Co-authors are Anindita Das, Ph.D. and Fadi Salloum, Ph.D. Author disclosures are on the abstract.

The National Institutes of Health funded the study.