JAK inhibitors show promise for CRC treatment

[Asterix]

I'm surprised this has come up yet.

http://www.abc.net.au/news/2014-10-01/d ... es/5783718

[NZJay]

Here is a link to a radio interview with one of the researchers:

http://www.radionz.co.nz/national/progr ... t-of-cases

[Wade0025]

Asked my onc about it today as I'm in Australia and he thinks it's very interesting. Hopefully it's the key

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Drug that stops bowel cancer growth in 80 per cent of cases uncovered by Melbourne researchers
The World Today By David Mark
Updated Wed at 7:21pmWed 1 Oct 2014, 7:21pm


PHOTO: Bowel cancer is the second largest cause of cancer deaths in Australia. (Flickr)
RELATED STORY: Sydney doctor claims poo transplants curing diseasesRELATED STORY: Promise check: Invest $46 million to bring forward biennial bowel cancer screening RELATED STORY: Tasmanians urged to take part in study of rare cancers
MAP: Melbourne 3000
Australian scientists have discovered a set of drugs that stop the growth of bowel cancers in about 80 to 90 per cent of cases.

Dr Toby Phesse, from the Walter and Eliza Hall Institute of Medical Research in Melbourne, said new forms of treatment for this type of cancer are in high demand.

"About 4,000 people are going to die of [bowel] cancer every year in Australia, and so we're really crying out for new therapies to try and target this disease," Dr Phesse said.

"And our lab is specifically looking for targeted strategies to try and work out which signalling pathways or which genes could be targeted to try and prevent this cancer."

AUDIO: Listen to David Mark's interview with Dr Toby Phesse (The World Today)
Dr Phesse said the team of researchers found a particular kind of drug called JAK inhibitors that can be used to target colon cancers.

"This particular pathway is regulated in many types of cancer, including colon cancer, and we found that 80 per cent of colon cancers have got a certain mutation in the weak pathway," he said.

"However, this pathway is also required for the normal cells of the intestine and so if you try and target that pathway directly, you pose a severe threat of actually affecting the normal cells of the intestine.

"So we wanted to try a different strategy and try and target a parallel pathway and that is what brought us to the JAK pathway.

"And we found that with the JAK inhibitors these tumours, 80 per cent of them, they were exquisitely sensitive to JAK inhibitors."

We just have to bring the story out now that these drugs actually can be used in colon cancer.
Dr Toby Phesse, Walter and Eliza Hall Institute of Medical Research
The drugs work in two ways: by stopping cell growth and, in pre-chemical models, preventing the development of new tumours.

"So this will be important for people who have got a familial condition in which they develop multiple intestinal tumours," Dr Phesse said.

"It's very exciting and it really opens the window now to use these drugs."

With JAK inhibitors already approved for use in other diseases, Dr Phesse expects the up-take of this new bowel cancer treatment to be quick.

"The great thing is that they are already existing in the clinic and they're being used to treat disorders such as psoriasis, arthritis, minor fibrosis," he said.

"So we don't have to spend the many years and the resources ... to develop a new drug.

"They're there in the clinic and we just have to bring the story out now that these drugs actually can be used in colon cancer."

Topics: bowel-and-rectal-cancer, medical-research, doctors-and-medical-professionals, health, cancer, diseases-and-disorders, melbourne-3000, australia

First posted Wed at 7:16pmWed 1 Oct 2014, 7:16pm

More stories from Victoria

[singingholly]

Thank you so much for sharing!

[janderson]

Thanks for posting. Very interesting and promising.

[sdp]

This is good. My question is which medicine should one take ( which is a jak inhibitor )
And what doses

[Asterix]

I spoke to my onc about this yesterday and he said that these results are in cell lines (test tubes) only. He said they have tried JAK inhibitors in studies but none have worked well in humans, which seems to contradict the media release saying there are already JAK inhibitors available. So I'm a bit confused.

[WifeOfMike]

I was just told this morning that a clinical trial using a JAK inhibitor is en-route to our trial clinic (not listed, not recruiting YET)
however it was also said it was going to be in combo with Stivarga- which my hubby already did without success
I will keep you posted when I know more, or see the actual trial(s) posted and know the real skinny (story)

HUGS,
Vicki

[ptfly]

I read the articles but not clear if this is for primary only? Is this tested for mets?
Paul

[WifeOfMike]

I don't think it has hit humans in clinical trials YET
But this IS the first I have seen JAK. I will be digging into it asap

I have also heard this is from our Aussie friends in Australia

[GrouseMan]

No - it has not been tested at all yet in combination with other drugs or alone, in humans against colon cancer, primary or mets. This is all preliminary work from what I can see. Far too early to tell if it will show any kind of benefit in people yet. There are at least two JAK inhibitors on the market that I am aware of. Both are used to treat autoimmune diseases. Several others are in development mostly for myelofibrosis though one is also targeting lymphoma.

See WIKI Article: http://en.wikipedia.org/wiki/Janus_kinase_inhibitor

A Listing of known Janus Kinase inhibitors: http://www.selleckchem.com/pathways_JAK ... oCD8bw_wcB

This isn't anything you are going to want to go out and get a prescription for right now unless you are adventurous. These drugs have their own set of potential side effects (one positive one is that it helps grow hair and or prevents hair loss!) And one black box warning is that the use of Tofacitinib could result in cancers and lymphoma. But since at least two drugs are already approved, a clinical trial can be put together much quicker than if these drugs were brand new and nothing known about their effects in people. So given funding - the group in Australia could likely start a small study pretty rapidly to see if there is anything to this.

Unfortunately too much of this sort of stuff pops up in the press likely too soon. It makes all our emotions jump up an down.

GrouseMan

[NZJay]

Unfortunately too much of this sort of stuff pops up in the press likely too soon. It makes all our emotions jump up an down.

GrouseMan

For sure. Just the sensationalist nature of media; there's surely no greater reader hook than "cure for cancer!!" Imagine being the one to break such a story.
To your average reader perhaps just an item of mild curiosity and aww wouldn't that be nice, but to people in the latter stages of disease this is the kind of potential that keeps some holding on. Sadly, that's all it ever seems to be; a vague future potential.

[oldegg]

Found this:

Study of Ruxolitinib in Colorectal Cancer Patients, ClinicalTrials.gov Identifier: NCT02119676
http://clinicaltrials.gov/ct2/show/NCT02119676?term=ruxolitinib+colon&rank=1

This is a JAK inhibitor by Incyte. They are looking at it for many cancers.
http://www.incyte.com/research/pipeline

[lizzy4k]

I am going to start this trial with stivarga (regorafenib) & Jaks (ruxolitinib) in about 3 weeks. I just quit a 9 week trial of Xeloda & Zaltrap - it didn't do much other than make me too tired to do anything, stomach cramps, etc. Scan showed some shrunk, some remained stable but some grew, CEA went up a bit (23 to 28).

So please post any info this trial if anyone else is going to do it. I just finished reading about some of your side effects with regorafenib and it worries me. I have never had either of these drugs. Starting to get tired of the side effects of them all!

Liz

[WifeOfMike]

Liz,

I posted quite a few experiences my hubby went through with Stivarga
IF you read some of the PREVENTIVE suggestions (the soaking of feet in room temperature water for instance) it MAY keep side effects from happening, or minimize the effects
Remember- not everyone gets side effects, and those that get them do not react exactly the same. I always advocated Preventative measures as the best course of action

I wish you nothing but the best for YOU in your clinical trial. I would love to hear of your progress, if you are up to it
It is people, like you and my hubby, that help everyone move closer to the day Colon Cancer is a totally treatable or Curable disease.
Best wishes,
Vicki