A potential cure made from girders ?!?!

Thanks Ian... just read the links and it all looks pretty hopeful- as you say the bit about autophagy is really interesting re: cell proliferation/death etc. "In CML, BCR–ABL mimics growth factor stimulation"

The Glasgow team look like they are seeing the fruits of their hard work into quiescence in CML stem cells. 

Thanks again for posting all the links- really interesting.

Doctors comment from March 2011:
http://esciencenews.com/articles/2011/03/30/new.approach.leukemia.chemotherapy.a.cure.sight

"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."

Sandy

Autophagy: ‘live & let die’

ChooseTop of pageCML therapeutics: ‘good, ...Autophagy: ‘live & let di... <<Hydroxychloroquine: ‘a ne...Complete cure of CML: hop...ConclusionReferences

As has been demonstrated in solid neoplasms, TKI treatment initiates the process of autophagy in primary CML cells [5]. Autophagy is a recycling process of vital cellular constituents, damaged organelles and harmful materials that is initiated following enclosure in double membrane-bound autophagy vacuoles (AVs) and delivery to lysosomes for proteolytic degradation. Autophagy can be initiated in starvation due to withdrawal of growth factor signaling. In CML, BCR–ABL mimics growth factor stimulation [6], thus its inhibition by TKI may induce autophagy in a similar fashion. Physiological autophagy is essential for cellular homeostasis and the death signal can promote cellular demise through autophagy, either independent of, or linked to apoptosis [7]. Although suppression of autophagy may be associated with cell transformation and carcinogenesis, malignant cells can also induce autophagy as a protective way to relieve therapy-induced stress as evidenced in CML after TKI treatment [5]. The decision between ‘survival’ or ‘death’ through induction of autophagy in malignancy probably depends on cellular context and signaling intensity [8]. Tackling ‘survival’ autophagy in CML [5] may therefore provide new hope for eradication of the disease. Chloroquine and Imatinib Combination to Eliminate Stem cells (CHOICES), a Phase II randomized clinical trial (ISCRTN No. 61568166) is currently completing a safety run-in period combining TKI with hydroxychloroquine (HCQ) before being opened further to patients in the UK.