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Old 09-17-2008, 04:39 PM   #1
eric
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HSP70 - 'Black sheep protein' key to cancer cell death

There's alot of good results with current HSP90 trials and it looks like HSP70 inhibitors can be even better...

http://www.news-medical.net/?id=41279

HSP90 inhibitors are a new group of drugs that work by stopping the activity of many cancer-causing proteins. After years of research, scientists found that silencing the HSP90 protein stopped tumours growing.
But now researchers funded by Cancer Research UK, and based at The Institute of Cancer Research, have found that inhibiting another protein in the same family - HSP70 - can help HSP90 inhibitors stop the growth of cancer cells and can also kill off tumour cells very effectively even without HSP90 drugs.
Their findings have led the researchers to believe that new drugs that inhibit HSP70 could be developed and used either on their own or in combination with HSP90 inhibitors - potentially providing more effective treatments that target cancer cells and leave healthy cells unharmed.
Lead author, Professor Paul Workman, based at the Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research in Sutton, said: "HSP70 proteins haven't received as much attention, and were the neglected members of the HSP family of proteins. When we silenced these proteins our results were really surprising."
The team studied the effects of silencing HSP proteins in bowel and ovarian cancer cells. They found that knocking out two particular proteins - HSC70 and HSP72 which are forms of the HSP70 protein - caused cell death only in cancer cells.
Professor Workman continued: "Most of the recent research in this field has focussed heavily on inhibiting HSP90, which was thought to be the most crucial protein involved in making sure cancer-causing proteins were kept intact. What's most exciting is that not only can knocking out both HSC70 and HSP72 eliminate the dangerous cancer-causing proteins, but in addition this approach can kill cancer cells much very more effectively than normal cells.
"We hope that in the future, drugs can be designed to inhibit the HSP70 proteins, following on from those that already block HSP90, to stop tumour growth and kill off cancer cells."
Professor Herbie Newell, Cancer Research UK's executive director of clinical and translational research, said: "This is a great example of why cancer research is such an exciting field. There are constantly new discoveries being made that challenge our current ways of thinking and that open up new doors for developing better and more targeted therapies.
"HSP90 inhibitors are currently being tested in clinical trials on patients with breast and other cancers. We hope this new research on HSP70 will be translated into exciting drug discoveries in the future."
http://www.cancerresearchuk.org/

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Old 09-19-2008, 09:32 PM   #2
Joan M
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Eric, Thanks. This is interesting. Sloan-Kettering is running a Phase I open-label HSP90 (CNF2024) trial. I had mentioned it to my local oncologist, but she was reluctant because it was Phase I. The trial has two groups of metastatic breast cancer, one HER2+ and the other HER2-.
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Diagnosed stage 2b in July 2003 (2.3 cm, HER2+, ER-/PR-, 7+ nodes). Treated with mastectomy (with immediate DIEP flap reconstruction), AC + T/Herceptin (off label). Cancer advanced to lung in Jan. 2007 (1 cm nodule). Started Herceptin every 3 weeks. Lung wedge resection April 2007. Cancer recurred in lung April 2008. RFA of lung in August 2008. 2nd annual brain MRI in Oct. 2008 discovered 2.6 cm cystic tumor in left frontal lobe. Craniotomy Oct. 2008 (ER-/PR-/HER2-) followed by targeted radiation (IMRT). Coughing up blood Feb. 2009. Thoractomy July 2009 to cut out fungal ball of common soil fungus (aspergillus) that grew in the RFA cavity (most likely inhaled while gardening). No cancer, only fungus. Removal of tiny melanoma from upper left arm, plus sentinel lymph node biopsy in Feb. 2016. Guardant Health liquid biopsy in Feb. 2016 showed mutations in 4 subtypes of TP53. Repeat of Guardant Health biopsy in Jana. 2021 showed 3 TP53 mutations, BRCA1 mutation and CHEK2 mutation. Invitae genetic testing showed negative for all of these. Living with MBC since 2007. Stopped Herceptin Hylecta (injection) treatment in March 2020. Recent 2021 annual CT of chest, abdomen and pelvis and annual brain MRI showed NED. Praying for NED forever!!
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