Can Someone Tell Me About Rapamycin and Treatment of Cancer?
Question by Kevin7: can someone tell me about rapamycin and treatment of cancer?
Best answer:
Answer by Ted H
MANTLE CELL LYMPHOMA
Sirolimus (INN/USAN), also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation. Recently, sirolimus was shown to inhibit the progression of dermal Kaposi’s sarcoma in patients with renal transplants. Other mTOR inhibitors, such as temsirolimus (CCI-779) or everolimus (RAD001), are being tested for use in cancers such as glioblastoma multiforme and mantle cell lymphoma. A combination therapy of doxorubicin and sirolimus has been shown to drive AKT-positive lymphomas into remission in mice. Akt signalling promotes cell survival in Akt-positive lymphomas and acts to prevent the cytotoxic effects of chemotherapy drugs, such as doxorubicin or cyclophosphamide. Sirolimus blocks Akt signalling and the cells lose their resistance to the chemotherapy. Bcl-2-positive lymphomas were completely resistant to the therapy; eIF4E expressing lymphomas are not sensitive to sirolimus.
http://en.wikipedia.org/wiki/Sirolimus#Cancer
BREAST CANCER
Feb 15, 2011 Scientists have discovered that resveratrol – a compound found in red wine – when combined with rapamycin can have a tumour-suppressing effect on breast cancer cells that are resistant to rapamycin alone. The study, conducted by researchers from Cleveland Clinic’s Lerner Research Institute, also indicated that the PTEN tumour-suppressing gene contributes to resveratrol’s anti-tumour effects in this treatment combination.
http://articles.timesofindia.indiatimes.com/2011-02-15/health/28546459_1_resveratrol-breast-cancer-red-wine
COLORECTAL CANCER
2009 Oct;13 The mTOR-inhibitor rapamycin has shown antitumor activity in various tumors. Bedside observations have suggested that rapamycin may be effective as a treatment for colorectal carcinomatosis. Rapamycin suppressed advanced stage colorectal cancer, even with oral administration. Combining rapamycin with current chemotherapy regimens significantly increased antitumor efficacy without apparent toxicity. The treatment efficacy correlated with serum TIMP-1 levels, suggesting its potential as a surrogate marker in future clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/19565301
LUNG CANCER (LAM) also KIDNEY AND LIVER CANCER
May 19, 2011 The drug sirolimus (also called rapamycin) has shown promise in the recent phase 1–2 trials involving LAM patients. It blocks mTOR activation and restores homeostasis in cells with TSC gene mutation. Lymphangioleiomyomatosis (LAM) is an rare systemic disease that destroys the lung and causes abdominal tumors. The disease is exclusive to women and is seen in 5 out of every million people. The disease occurs sporadically. Typically in patients with LAM, the lung function declines and hypoxia develops within a decade of symptoms appearing. Smooth-muscle cells infiltrate the lung of LAM patients. They arise from an unknown source and appear to be histologically benign. These cells show the presence of TSC gene mutations. This results in activation of the mammalian target of rapamycin (mTOR) signaling pathway. This pathway regulates multiple cellular functions and controls growth, motility, and survival. In rodent models of TSC gene mutation, sirolimus has shown to cause regression of neoplastic growths in the kidney and liver.
http://www.medindia.net/news/healthwatch/Sirolimus-Effective-in-Treatment-of-a-Rare-Type-of-Lung-Cancer-LAM-85214-1.htm
PANCREATIC CANCER
MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity.
Cancer research (2010) Rapamycin treatment suppresses pancreatic tumor development.
http://aspenbio.wordpress.com/2011/10/22/new-pancreatic-genomics-papers/
VALPROIC ACID AND RAPAMYCIN SHOW POTENTIAL ANTI TUMOUR EFFECT
02 Mar 2011 Two existing drugs valproic acid and rapamycin have the potential to play a role in the treatment of cancer by interfering with the DNA damage response mechanism, reports a study from the Istituto FIRC di Oncologia Molecolare (IFOM) and the Istituto Europeo di Oncologia (IEO) in Nature.
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Drug Development News from IAS2011 – Cal Cohen, MD, gives a brief synopsis of the drug development news from the International AIDS Conference in Rome, July 2011.