Personalised Treatment

[pog451]

Im not at all sure if there is anything new behind this, or if it isn't just a summary of advances we've heard of before, but its interesting that it has penetrated far enough into the mainstream to be reported in a tabloid newspaper (in this case the UK populist conservative "Daily Mail")

http://www.dailymail.co.uk/health/artic ... chers.html

Whaddaya think, guys n gals?

[Oneeyeddog]

I saw this a few weeks back, pog.

http://www.cancerresearchuk.org/about-u ... wel-cancer

Looks quite interesting.

[Maia]

Here there is a more detailed explanation
http://www.cancerresearchuk.org/cancer- ... erFriendly

Looks like they are putting to use the possibilities of genetic tumour profiling!

[GrouseMan]

Here there is a more detailed explanation
http://www.cancerresearchuk.org/cancer- ... erFriendly

Looks like they are putting to use the possibilities of genetic tumour profiling!

In my opinion this is the way to go with cancer treatment. It may more precisely target the tumor and provide a greater selection of approaches. It certainly can't hurt. The only problem is that genetic profiling is expensive to do.

GrouseMan

[some]

GrouseMan,

How expensive is it? I ask that because the chemo which is expensive too may not work and that's money down the tubes. If this allowed for better treatment, it could save people which is so much better than just treatment, though I suppose that living longer could cost the insurance company more. I sure hope they don't look at it that way.

Thanks.

Serena

[Maia]

In my opinion this is the way to go with cancer treatment. It may more precisely target the tumor and provide a greater selection of approaches.

Yes, yes!
The same goes for knowing more markers beyond CEA, to monitor.
When my friend went to the SCCA (WA), they ran a genetic sequencing on a tumour sample (they got her local hospital, in Toronto, to send the slices to them). I *think* it was not quite expensive, and it was part of her visit to an oncologist there. The results take 2 months. It's a particular development of the University of Washington, called Oncoplex:
http://www.seattlecca.org/diseases/onco ... erview.cfm

This is more technical information:
"UW-OncoPlex is a multiplexed gene sequencing panel that detects mutations in tumor tissue in 194 cancer-related genes (listed in the methods below). The panel includes genes related to cancer treatment, prognosis, and diagnosis. The test uses next-generation "deep" sequencing to detect most classes of mutations, including single nucleotide variants, small insertions and deletions (indels), gene amplifications, and selected gene-fusions." http://tests.labmed.washington.edu/UW-OncoPlex
It looks like doctors from other facilities can order it too.

[Redtexa5]

Carl Icahn donated 200 million dollars to Mt. Sinai in NY City to fund research on gene sequencing and Steve Jobs had his tumor genetically sequenced. There is quite a bit of research going on along these lines and not just for cancer treatments. As you might expect, much of the research is aimed at lowering the cost of the sequencing and they seem to be having some good results.

Here is a link to an article that talks about an application of Mt. Sinai's research, but it is a ways from being the standard of care.
I think this link was posted by someone else previously, but I think it is interesting.

http://www.esquire.com/features/patient-zero-1213

[rp1954]

Some personalization has been long overdue with the markers we already have, starting with CA19-9, CEA, vitamin D and inflammation markers on the first day of diagnosis, along with fully extended blood chemistry panels. A lot of what is being promoted in the press for personalization seems more about advertising and high prices on marginal drugs and services.

The other under utilized personalization techniques concern viable tissue tests like Weisenthal Cancer Group and Rational Therapeutics do, nearly invisible in most cancer center practices.

[Laurettas]

My husband had testing done on his cancer through Caris and the cost was under $10,000. Given that if it had been done earlier and his BRAF mutation had been discovered, it would have saved over $100,000 in expense for Erbitux. Plus it showed that the standard chemo drugs were not going to be effective either so could have saved even more money on the other drugs. Not to mention the suffering my husband went through receiving those drugs and the waste of time that we could have spent doing something worthwhile with the time he had left.

[GrouseMan]

GrouseMan,

How expensive is it? I ask that because the chemo which is expensive too may not work and that's money down the tubes. If this allowed for better treatment, it could save people which is so much better than just treatment, though I suppose that living longer could cost the insurance company more. I sure hope they don't look at it that way.

Thanks.

Serena

Sorry - I think someone else has given a good accounting of the cost/benefit ratio. But be aware also that these screens are rather limited at moment and largely look for known mutations seen before, and even then not the specifics for what substitution/or truncation is involved in the mutation. A very detailed sequence analysis I think would cost much more than $10K. Also be aware that tumor genes change over time due to chemotherapy and radiation therapy as well. So over time the mutations may change, so its a good idea to check again. Also - Mets may have different mutations than the primary tumor from which they came. So all this complicates the picture.

The Mt Sinai group I am really impressed with. But they do go the extra mile and profile the tumor in detail as well as create fruit fly models of the genetic changes and then test drug combos on those fruit flies! Its truly a personalized treatment as the fruit flies are stand ins for your unique set of mutations for testing out the initial drug combinations!!! This is mostly research, and they are in no way able to do this for everyone. But they hope to gather enough information eventually, were they can make broad though much better predictions on how to treat cancer based more on genetic markers than bulk pathology of colon vs breast vs lung etc...

Eventually I believe we will see a positive shift in how we treat people's cancers. More towards the individual end of the spectrum as time goes on. I think trials will also eventually be shorter and more targeted to determine safety as apposed to comparing treatments in large groups of people initially. We may end up with many more drugs used in greater combination.

GrouseMan

[lohidoc]

Not to rain on anyone's parade, but I am extremely sceptical about this approach. No doubt it is interesting to decipher the genome of cancer tissue, no doubt it will add a little to our understanding, and perhaps it may even help, up to a point, to rationalize treatment.

But it will not lead to any truly effective treatments because the premise is wrong and based on an insufficient understanding of cancer.

Cancer that has existed for a period of time (and advanced, metastatic cancer by definition falls into that category) exists in a state of mutational chaos. These cells have undergone so many mutations, acquired so many pathways and characteristics that it is impossible to catalogue them or understand all of them. Many cancer cells contain up to 96 chromosome pairs. In any one patient a variety of cell clone populations will exist, each with different characteristics.

The notion that a biopsy can be done, that the tissue can be analyzed and a rational and effective treatment be provided does not hold up. It is as if one could rip a handful of random pages from a novel, and believe that on the basis of that the book can be known. Analysis of the original tumour will not accurately describe the characteristics of the same cancer years later.

What this approach will do is increase funding for those involved in it, many papers will be published and reputations will be made. My own hospital has recently acquired funding for this type of research, and a very nice young scientist has been appointed.

Here is an example: In 1979 David Lane discovered the P53 gene. Since then more than 65,000 papers on this gene have been published, at an estimated cost of $6.5 billion. Our understanding of this gene remains incomplete, no therapies have emerged from all this.

Even if the premise was correct, the dysfunctional way in which cancer research is organized makes it unlikely that anything really useful will emerge. As an example, one obstacle here is the acquisition of tissue samples for analysis. There is no national database for cancer tissue. Most research institutes jealously guard the material they have, and won't share with other institutes. For ten years attempts have been made to create a national tissue bank. Not a big deal you might say, all it takes is for the "stakeholders" to come to an agreement. But we are no further in this than ten years ago. Ego, turf protection, bureaucratic inertia. As a result, a critical mass of tissue to be studied cannot be obtained and only small, piecemeal and uncoordinated progress will be made, at, of course, a huge cost.

The "IT" drug is Gleevec, the central drug in the new theology of cancer, which started all this. Gleevec is an antibody specifically designed to disrupt a tyrosine kinase pathway that causes a cancer known as Chronic Myeloid Leukaemia. A relatively rare cancer, with a poor prognosis, it is unique in that , in its earlier stages anyway, it has one single mutation that turns white blood cells cancerous. Gleevec disrupts this aberrant pathway, and patients who respond now have an almost normal life expectancy. And everyone, and every company is now looking for the next Gleevec, ignoring the unique characteristics of CML.

For those interested in how cancer research functions I recommend "The Truth In Small Doses" by Clifton Leaf.

[Maia]

Not to rain on anyone's parade, but I am extremely sceptical about this approach. No doubt it is interesting to decipher the genome of cancer tissue, no doubt it will add a little to our understanding, and perhaps it may even help, up to a point, to rationalize treatment.

But it will not lead to any truly effective treatments because the premise is wrong and based on an insufficient understanding of cancer.

My parade is still dry -because it's an immunological one, as you know very well. For me (just my opinion, I'm not a chemist, doctor, scientist of any kind) the future of cancer treatment is immunotherapy, as many may guess from my posts, not tumour profiling. But, because of the way some immunological clinical trials are being designed right now (combining somehow 'pure' immunotherapeutic agents with something else), it's apparent to me that we may need also some agents that are not biological to target certain pathways -like RAF and MEK inhibitors, PI3K-related drugs, for example. Why can't the immune system have a a little help from its friends. : )

My agreement with GrouseMan about 'this is the way to go with cancer treatment' was with that, treatment , --not research. (Of course the research on the genome of cancer tissue should continue... but for the reason I've stated!: because the emphasis of research should be in immunology and cancer, and all this knowledge would be ancillary to it).
What I meant was that, right now, today, and from a patient/ caregiver perspective, in the ongoing treatments, it happens what Lauretta described -drugs, usually expensive, given with no benefit or that may be harmful (see past week news: cetuximab worsening outcomes, when given along chemo to liver resectable patients, maybe because nobody ran a panel, we don't know right now). Also, there are opportunities missed: we *do* have, right now, some tools to target those pathways. Why an unresectable mCRC has to be offered the usual (and usually, miserable) path (1st, 2nd, 3rd line... Folfox - Folfiri -regorafenib/aflibercept... end or road) if he/she has, for example, a BRAF V600E mutation? Right now, understanding it's off label use, he/she could receive treatment with trametinib (MEK inhibitor FDA approved for BRAF V600E mutated melanoma) or dabrafenib (BRAF inhibitor, also approved as single agent for melanoma). Better than being hit with oxaliplatin, probably.
When I replied to GrouseMan, I was just being patient-oriented and having in mind my friend's Oncoplex results: KRAS mutated, that she already was aware of, but other was PIK3CA mutation, so the interpretation was "In patients with colon cancer, activating mutations in PIK3CA have been associated with responsiveness to aspirin therapy (Liao X, et al. Aspirin use, tumor PIK3CA mutation, and colorectal cancer survival. N Engl J Med. 2012, 367:1596. PMID 23094721)". Not a big thing but just 'yes, take aspirin that, in your case, there are chances that it will help". I don't think she showed this report to her oncologist, but that's other story.

About how cancer research works, I only can agree. It's sad. I'm certainly looking for Clifton Leaf's book.
On a side note, I was reading an article published past Wednesday, about Jim Allison. You may like that. The 4 pages are worth reading; just in the first, you have him confessing: "People would say to me, 'Don't do tumor immunology, it'll ruin your reputation.' Jim Allison confronts cancer, critics with immunotherapy

[juliej]

On a side note, I was reading an article published past Wednesday, about Jim Allison. You may like that. The 4 pages are worth reading; just in the first, you have him confessing: "People would say to me, 'Don't do tumor immunology, it'll ruin your reputation.' Jim Allison confronts cancer, critics with immunotherapy

Ah, Maia, you're talking about one of my favorite people, Dr. Allison! He is the former director of the tumor-immunology program at Memorial Sloan-Kettering. I know several people who are alive today because of ippy.

Your link doesn't work so here's a new one: http://www.sfgate.com/health/article/Jim-Allison-confronts-cancer-critics-with-5405290.php

And here's another (older, but good) article that mentions him and other work on immunology: http://www.newyorker.com/reporting/2012/04/23/120423fa_fact_groopman?currentPage=all

[Laurettas]

Because releasing the brake facilitates an all-out attack by the immune system, it can cause serious side effects - colitis, skin rashes, impaired pituitary function - that must be managed.

This is what concerns me about this type of treatment. If the immune system is allowed to go on the attack with no brakes, couldn't that be devastating on the body? Aren't MS, some types of arthritis, etc. all the result of overactive immune systems? Are we opening the door to many more of these types of incurable illnesses?

[Misha]

On a side note, I was reading an article published past Wednesday, about Jim Allison. You may like that. The 4 pages are worth reading; just in the first, you have him confessing: "People would say to me, 'Don't do tumor immunology, it'll ruin your reputation.' Jim Allison confronts cancer, critics with immunotherapy

Ah, Maia, you're talking about one of my favorite people, Dr. Allison! He is the former director of the tumor-immunology program at Memorial Sloan-Kettering. I know several people who are alive today because of ippy.

Your link doesn't work so here's a new one: http://www.sfgate.com/health/article/Jim-Allison-confronts-cancer-critics-with-5405290.php

And here's another (older, but good) article that mentions him and other work on immunology: http://www.newyorker.com/reporting/2012/04/23/120423fa_fact_groopman?currentPage=all

I read that great article in the Houston Chronicle two weeks ago. My mom is stage IV mCRC and will be at MDA on Monday. Does anyone know if Mr. Allison has any clinical trials accepting patients. I looked around, but could not find anything.