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New approach to leukemia chemotherapy -- is a cure in sight?


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#1 CallMeLucky

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Posted 31 March 2011 - 12:20 PM

This is the first I have read about this approach using hydroxychloroquine.  Wonder if it will lead to anything

http://www.eurekaler...s-nat033011.php

Speaking at the UK National Stem Cell Network conference in York later today  (31 March), Professor Tessa Holyoake from the University of Glasgow will discuss  a brand new approach to treating chronic myeloid leukaemia (CML) in which a  small number of cancer cells persist despite effective therapy thus preventing  cure.

CML is a type of blood cancer caused by the infamous "Philadelphia  Chromosome" genetic abnormality. It is usually treated using a class of drugs  called Tyrosine Kinase Inhibitors and in the majority of cases this treatment is  successful, with around 90% of patients recovering from the disease. However in  the majority of patients a subset of cancer cells - CML stem cells - are  resistant to Tyrosine Kinase Inhibitors.

"At the moment we are working with 9 patients who still have low level  evidence of CML despite Tyrosine Kinase Inhibitor treatment. They are helping us  to test the use, in principle, of a new type of drug that specifically deals  with the resistant CML stem cells," said Professor Holyoake.

"The drug we are using in the trial is hydroxychloroquine - a well  established antimalarial drug that has been used commonly since the 1950s and is  also used in rheumatoid arthritis. This will allow us to test the principle of  using similar drugs to treat CML patients.

"Unfortunately hydroxychloroquine may not be suitable for very long term  treatment because of side effects. In particular there is a very low risk of  temporary or permanent eye problems. In our trial the patients will take the  drug for up to 12 months with very close monitoring of their eye health, which  will allow us to intervene at the very earliest sign of an adverse effect,"  Professor Holyoake continued.

The patients in the trial have already taken a Tyrosine Kinase Inhibitor drug  for at least a year, which has reduced the number of cancer cells in their blood  to a very low level.

Professor Holyoake's team discovered that CML stem cells avoid the impact of  Tyrosine Kinase Inhibitor treatments by going into a state called autophagy in  response to the drug. This means that they begin to shut down and use nutrients  from within the cell to survive in what is effectively suspended animation. In  this state the drug cannot kill them and so later they can initiate a resurgence  of the disease. Hydroxychloroquine has been shown to kill cells that are  undergoing autophagy and the trial is designed to test whether this is a  potential route for treatment in patients.

Professor Holyoake concluded "Although hydroxychloroquine probably isn't the  final answer for treating resistant CML stem cells, we are aware that there is  interest from the pharmaceuticals industry in developing new drugs that target  cells undergoing autophagy. We are therefore very hopeful that once we can prove  that in principle this approach works, it could lead relatively quickly to a new  treatment for patients for whom Tyrosine Kinase Inhibitors don't provide a full  cure."


Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%
 

 


#2 jrsboo

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Posted 31 March 2011 - 12:25 PM

Hmmm, I wasn't aware that the TKI's were providing a full cure in anyone............(last line of story: it could lead relatively quickly to a new  treatment for patients for whom Tyrosine Kinase Inhibitors don't provide a full  cure.").  But if it works, that would be terrific news!  Thanks for the heads up, Lucky!

C



#3 rickpister

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Posted 01 April 2011 - 09:45 AM

Hydroxychloroquine is a welcome possibility considering the $8,000 a month Sprycel demands.  I am looking forward to seeing how this pans out.






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