A Ship Called Titanic

If i'm on a ship called Titanic, I'd be busy reading up on "Sailor's guide to icebergs" or "Surviving shipwreck for dummys".    I'd be running around calling out to everyone to get on improvising a lifeboat or thermal suit or start to acclimate to cold water.    I would be the oddest character in the movie.  I will not be enjoying life to the fullest, whatever that means.   And until that Titanic docks safely, I'll just delay my partying a bit.

Imagine Kate telling Jack in cold water: "Jack you need to have a positive attitude".    Well I keep getting that from well meaning people.  

Failing lungs? No problem

Here's your oxygen shot straight to your blood stream:

http://www.popularmechanics.com/science/health/breakthroughs/no-lungs-required-injected-oxygen-
to-keep-patients-alive-10087551

A lot of kinks to work out, also a bridge solution that solves 10 minutes in crisis situation.   But cool idea nonetheless.  

Deserve to Die

Think it's for lung cancer.   It's an interesting campaign

http://digg.com/newsbar/topnews/deserve_to_die_posters_pop_up_in_some_u_s_cities

Human Microbiome Project

NYT comes out with a couple of gems related with the bacterial ecosystem inside us.

 

http://www.nytimes.com/2012/06/14/health/human-microbiome-project-decodes-our-100-trillion-good-bacteria.html?pagewanted=all 

This kind of study was impossible/very expensive to do just a few years ago.   But now it produces wealth of information.     First on healthy people and healthy bacterias.   Some day for cancer patients and bacterias.   I wonder if there's difference.

 

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=all

 

Imagine the researchers presenting their poop-transplant results with a straight face   And their beaming parents and their proud offsprings.   ROFL.

Let me jump aboard my hobby horse again.   Support research, support clinical trials and donate your *samples*.

A long thread on BCO about this and canine oncologist:

http://community.breastcancer.org/forum/73/topic/789218

Interesting TED talk about multilingual bacteria

http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html

and another TED talk about an immortal cancer that is passed from one animal to another.

http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html

 

Finally, clinical series live with some very interesting talks:

http://www.clinicalserieslive.com/login

Neoadjuvant clinical trials and anti-metastasis clinical trials

New anti-metastasis trial design, alternative better cheaper cures:

http://www.cancer.gov/ncicancerbulletin/061212/page4

New neoadjuvant clinical trial design for early stager newly diagnosed patients, faster cheaper clinical trial for the cure, sooner rather than later:

http://ispy2.org/

FDA and scientists are doing their job, trying to find the cure sooner and cheaper.   They need patients to learn about these new trial designs and spread the word. Every women should hear about it, especially high risk women before diagnosis, and newly diagnosed. Neoadjuvant = pre-operative. anti-metastasis would help everybody, including current stage IV.

Tumor Tissue Donation

I looked around in clinical trials for keywords like "genome", "microRNA", "tumor tissue", "tissue bank", "cell line", "dna", and of course "breast cancer".   You could also look for "NCI".   In looking for trials, look for NCI sponsored trial if possible. And ask for data sharing among researchers.

http://clinicaltrials.gov/ct2/show/NCT00032201?term=breast+cancer+tissue+banks&rank=18

This one is creating cell lines from high risk breast tissue. if you had breast cancer before, your noncancer breast tissue might be immortalized! "To establish a repository (facility in which tissue samples can be preserved and stored for many years) of cell lines from high-risk breast tissue to allow researchers to learn more about changes in breast cells that may cause them to develop into breast cancer."

http://clinicaltrials.gov/ct2/show/NCT00899301?term=tumor+tissue+breast+cancer+DNA&rank=16

http://clinicaltrials.gov/ct2/show/NCT00899509?term=tumor+tissue+breast+cancer+DNA&rank=10

http://clinicaltrials.gov/ct2/show/NCT01000883?term=tumor+tissue+breast+cancer+DNA&rank=15

http://clinicaltrials.gov/ct2/show/NCT01334021?term=genome+breast+cancer&rank=4

http://clinicaltrials.gov/ct2/show/NCT00897702?term=genome+breast+cancer&rank=16

http://clinicaltrials.gov/ct2/results?flds=Xh&flds=a&flds=b&flds=c&flds=g&flds=j&term=breast+cancer+microRNA&show_flds=Y

http://clinicaltrials.gov/ct2/results?flds=Xh&flds=a&flds=b&flds=c&flds=g&flds=j&term=breast+cancer+tissue+banks&show_flds=Y

Prediabetes + Breast Cancer

I just found out I'm prediabetic with impaired insulin resistance.

Here are the things I found out:

About 20% of people 20 years and older are prediabetic.  

http://diabetes.niddk.nih.gov/dm/pubs/statistics/#Pre-diabetes 

Prediabetic patients get BC at about 3 times the rate of normal population

http://www.cancernetwork.com/conference-reports/asco2011/content/article/10165/1874808 

http://www.usatoday.com/yourlife/health/medical/cancer/2011-01-22-breast-cancer-diabetes_N.htm 

Prediabetic patients should be treated with metformin and get on low starch diet/exercise.   So check your blood sugar to make sure you are not prediabetic.

http://tristarpub.com/endo2011/?p=90

Friday Laugh

This story is supposed to be somewhere near Afghanistan:

young woman:   Auuugh, I heard my chance of dying in child birth is 5% per delivery.   

woman's mom says:  That's cruel!   Who did such a cruel study!  All women are individual with individual risks!

young woman:  1% or 5%.  I still don't wanna die!

woman's mom: My dear, look at this as a glass half-full situation, 95% chance you'll be ok!   Life is beautiful and pink.   The sunshine so nice.   Look at every day as a blessing...   In my mother's day, the chance of death was 10% per delivery.    Wait, let me be positive, in my mother's day, the chance of life was 90%!

young woman:  I need to do something about it.    try to improve the hospital conditions for example or join a clinical trial!

woman's mom:  I'm so sad.   You have a beautiful future that's 95% sunshine, why do you persist in dwelling on the negative.

[It goes on on and on]

Stem Cell Conference in Japan

EU is debating cutting Embryonic Stem Cell funding.   Leading scientists asked for continued funding:

http://www.forbes.com/sites/johnfarrell/2012/06/15/stem-cells-in-the-news-and-yokohama/

Science/medicine is accumulative.    All the therapies we took granted today were built on top of sweats and blood and suffering of people and animals.   We have a debt to repay and an investment to make.

Also a FDA regulation viewpoints by forbes:
http://www.forbes.com/sites/gerganakoleva/2012/02/19/stem-cells-fda-and-the-edge-of-science-three-expert-viewpoints/

Recurrence rate and stage IV survival rate: UK Study

Depression Alert!!!!   Don't read it if you don't like ugly, cruel, barbaric stats.   It's about a sneaky, ugly, cruel, barbaric disease called metastatic breast cancer:
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http://www.guardian.co.uk/society/2012/jun/12/breast-cancer-recurrence-study-macmillan?newsfeed=true

Notice for early stagers diagnosed around 2000, 10 year recurrence rate is 20+%.  AND the worse than recurrence rate: the life expectancy of the recurred patients: they survived for an average of 17.9 months after being diagnosed for a second time.

Breast cancer has no cure/survivors, ladies, sorry to pop your pinkwashed bubble.    The chemos you are on are mostly 20,30 years old.    The hormone therapies you are on are 10-30 years old as well.   Herceptin is 10+ years old.   Newer drugs extend life by months, not even years, let alone decades.

Prevention is an expensive deadend that took 30 years to get to this.   Support metavivor or metastatic breast cancer research and join clinical trials.   Try earmark your donation to go straight to scientists/graduate students or specific research. 

Whacky Idea 2: Oncolytic Virus

In news yesterday, oncolytic virus (reovirus) hitch a ride to kill cancer cells:
http://www.medicalnewstoday.com/articles/246619.php

Keypoints:

a.  they found virus replicating factory inside the tumor

b.  they didn't find the virus replicating factory in normal tissue.

c.  the virus evaded immune system 

Because virus can be engineered to add a little gene to create a potent cancer toxin, so reovirus become a perfect delivery system.

But c. is also scary.  and b. is important for the safety of patient. 

----------------   Whacky idea alert -------------------------------------

What if we re-engineer a mastitis virus, something that home into breast cancer cells to replicate inside a breast cancer cell? 

http://www.slideshare.net/Oncos/cgtg102-oncolytic-virus-in-breast-cancer-iir-conference-may-5-2010-3964027

Other gene therapy platform:
http://www.mdanderson.org/newsroom/news-releases/2011/gene-therapy-kills-breast-cancer-stem-cells-boosts-chemotherapy.html

Whacky Idea I: Thank you Berlin Patient

So the Berlin Patient, the 1 patient in the world who was cured of AIDS, got me thinking.  

What if, we find some highly effective breast cancer resistant gene, which could be an immunity gene X (Metabric study already identified some, should be more by other researchers).   Then we find a patient with both BC (preferably MBC) and leukemia, call her P.   Because P needs bone marrow transplant anyway, we gave her a donor's bone marrow who happened to have breast cancer resistance gene X.  

This idea is similar to cancer vaccine, just a little more far fetched.  

AIDS has a cure. Where is the MBC cure?

A man Brown with AIDS developed unrelated leukemia. 

http://nymag.com/health/features/aids-cure-2011-6/

http://news.yahoo.com/study-digs-secrets-keeping-hiv-check-180404115.html

Quote:

Only about one in 200 or 300 HIV patients is able to naturally keep the virus from developing into AIDS without the help of medications. 

...

 After chemo, the leukemia came back. Brown's last chance was a stem-cell transplant from a bone-marrow donor. Hütter had an idea. He knew little about HIV, but he remembered that people with a certain natural genetic mutation are very resistant to the virus. The mutation, called delta 32, disables CCR5, a receptor on the surface of immune-system cells that, in the vast majority of cases, is HIV's path inside. People with copies from both parents are almost completely protected from getting HIV, and they are relatively common in northern Europe-among Germans, the rate is about one in a hundred. Hütter resolved to see if he could use a stem-cell donor with the delta-32 ­mutation to cure not just Brown's leukemia but also his HIV.

Hütter found 232 donors worldwide who were matches for Brown. If probabilities held, two would have double delta 32. Hütter persuaded the people at the registry to test the donors for the ­mutation; his laboratory paid, at a cost of about $40 per sample. They worked through the list. Donor 61 was a hit.

Notice how tentative the man's leukemia doctor was. He did not know that much about HIV but made a connection and a leap of imagination, went through a lot of extra nonstandard procedure to get his patient the perfect donor.    The patient, Brown, with the help of transplantation, is now "cured" of HIV.    Brown doesn't even need to take antiviral cocktails that already gives HIV patients near normal life expectancy.    

The story is compelling.   Please take a moment to read through them.

What does it mean for breast cancer patients?   Note how AIDS, even without cure, has life expectancy of 63 year old, while MBC patients has life expectancy of a few years/months from diagnosis.    Yet, some MBC patients with certain immunity genes have the best prognosis for BC.   One day these genes can be figured out and maybe a cure.   For this day to be soon, patients and doctors and researchers need to work together.

More quotes from nymag:

---------------------- 

For Brown's cure to be relevant on a wide scale, it would have to be possible to create the delta 32 mutation without a donor and without a transplant-preferably in the form of a single injection. As it happens, progress toward that goal has already begun, in the laboratory of Paula Cannon at the University of Southern California. Instead of a donor, Cannon is using a new form of gene editing known as zinc finger nucleases, developed by the California company Sangamo BioSciences. Zinc finger nucleases are synthetic proteins that act as genetic scissors. They can target and snip a specific part of the genetic blueprint: They can, for instance, cut out the code that produces the CCR5 receptor, yielding a cell with HIV resistance.

---  End quote 

Genetic therapy is a direction that needs to be pursued for MBC.   The same article also mentioned a HIV charity on a used-car sized budget trying to drum up enthusiasm for the HIV cure, how the idea of cure was met with great skeptism and self-doubt even by Hutter, and how this case of cured AIDS patient (by an obscure doctor who knew little about AIDS) for years received little notice from the AIDS scientific cycle or the broad public, .

I think this story has great deal of relevance for the search for MBC cure, and is a great inspiration for patients/activitists/doctors/researchers alike. 

All newborn babies are ugly

Early stage cancer cures are ugly for a long time.   Pertuzumab failed as a single agent cure, succeeded in multi-agent therapy.   Everolimus failed as a single agent breast cancer drug, succeeded in multi-agent therapy.  Herceptin was almost cut by Genentech before clinical trials.  The list goes on and on.


Now here's another ugly one:

http://www.cancertodaymag.org/Spring2012/Pages/blocking-metastatic-disease.aspx?Page=1

"Despite Psap's promising start, however, Watnick cautions that the first clinical trials of any such drug in people are at least two years away. It's also possible that his passionate investment could turn out to be a false start: Researchers have found thousands of molecules connected in some way to the spread of cancer. Most of these molecules never turn into plausible targets for cancer treatment-though a select few continue to advance slowly toward becoming potential new therapies. " 

But the idea is an interesting one:  can you stop metastatic cancer by something made by nonmetastatic cancer?   The PI is looking for investors.      

Folate-Receptor Alpha: Drug target

A new folate-receptor alpha vaccine is going to clinical trial at Mayo:
http://clinicaltrials.gov/ct2/show/NCT01606241?term=mayo+folate+breast+cancer+vaccine&rank=1


This is the paper I found by the PI:
http://jco.ascopubs.org/content/24/26/4254.full.pdf


It goes into the peptide vaccine's composition and the folate receptor target is also expressed in small mounts in kidneys.   So people with autoimmune problems or kidney problems may need to be careful (excluded in the clinical trial).    


Overall vaccines tend to have low toxicities so hope this trial would recruit easily. 


Another strategy that can target folate-receptor alpha is similar to TDM-1's conjugate strategy:
http://www.springerlink.com/content/yv05130861863525/ 


A lot of work needs to go into how to shuttle the chemo through the receptor-binding into the cancer cells, and unload the chemo once inside.    

I'm also reading a book "Emperor of illness",   it told of the story of Herceptin.   If not for the dedication and risk-taking of a small band of scientists/advocates/patients, Herceptin would not have been invented, or its adoption would have been signficantly delayed.    

 

In fact, in every major development in cancer cure chronicled in this book, personal passion and risk taking played a significant role.   So when I see early projects like this, I ask myself, what can I do to help?   As a patient, the least I can do is

1.  I can educate myself on different clinical trials and participate in relevant clinical trials.   Donate my patient record/tumor samples to researchers

2.  Instead of buying a fancy wig or eat something unhealthy, I can donate to a metastatic breast cancer fund or directly to researcher that's working on something earlystage but interesting.    My vanity/sweet tooth budget can go to research :-)

3.  I can share information with other patients

 

CTC: prognostic marker in early stage BC

http://www.mdanderson.org/newsroom/news-releases/2012/md-anderson-research-finds-predictive-value-of-circulating-tumor-cells.html

The next step is to be able to molecular characterize the CTCs (Her2, ER/PR, other receptors, mutations) and guide treatment strategies realtime and accelerate clinical trials.

This sentence gave me pause: "Of those, 15 per cent experienced a cancer relapse and 10 per cent died during the study period" in 5 years study period 2005-2010.   5 year mortality rate of about 66% among these early breast cancer patients with 1 + CTCs.   This is at MD Anderson.

"For women with three or more circulating tumour cells in their blood sample, the outcomes were much worse: 31 per cent died or experienced a relapse." 

This is why the research for MBC cure needs to accelerate.   20 years, the improvement in MBC mortality rate has gone from 97% to 66%.   MBC is not "chronic" like AIDS or diabetes.   AIDS or diabetes patients can expect to live a full life span.   MBC is a killer with no cure.  and no early stage patient is really cured till MBC has a cure.

CTC test is not without problems.

CTC test needs special tubes and needs mixing the blood carefully after blood draw.   Also it needs to be run 2-3 days after the blood draw.   

Also,  CTC has high false-negative rate.  ie, only a portion of metastatic patients get positive CTCs.   The next generation of CTC test hopefully will lower that false negative rate, and become more accurate.

But for fast clinical trials, CTC can be an useful tool.   Say you take only patients with 5+ CTCs, gave them experimental medicine and see whether the CTC drastically drops and stay dropped.   Patient commitment: a course of experimental medication.   Researcher gets results in a few days/weeks can go on to the next iteration of experimentation with dosage or drug design.   Cost would be much less than current clinical trial cost design.   There will be more drug companies testing more drug candidate for cheaper.   End result:  the cure.

I'm sure the doctors would say "this is not ready for prime time".   Doctors can be as cautious, caution being the intersection of  lawsuit and scholarship cultures.   But hey, 10 years later when it's ready for prime time,  a lot of patients would have died for want of the cure, and MBC mortality rate would drop from 66% to 50%?

Dying patients do not wait for prime time. 

Do you want data integrity or save patients lives?

Very interesting article on the trade-off:

www.forbes.com/sites/matthewhe...

However, I am not sure it covers all the costs of a more lengthy process that tries to ensure data integrity.   Faster, cheaper processes leads to faster/cheaper drugs, and ultimately more effective drugs.   The cost in delaying the process (more data integrity) lies in

I think this article does not cover all the costs of a more lengthy process that tries to ensure data integrity. Faster, cheaper processes leads to faster/cheaper drugs, and ultimately more effective drugs. The cost in delaying the process (more data integrity) lies in

1.  the patients' lives endangered,

2. more difficult recruiting of patients into randomized clinical trials.  Patients who put their lives on the line to go through the blinded trials.  When they hear the preliminary data that's highly promising but may be just a little short, they need to make the choice of dropping out of clinical trials if they are in the control arm vs staying in the control arm, and die to make the OS (overall survival) data true.   That is difficult choice for patients and physicians, and difficult for any future double blind clinical tials to recruit.

3. in the ultimately higher cost of drugs.

Note how almost all the drugs that had early terminated drug trial end up being highly effective and lifesaving.    If a couple of drugs later turned out to be less effective than originally thought, it's not a big deal.    The statistically significance standard for treatment for end-stage cancer with no other options  should take into account the benefit for patients, and be different than the standard for treating something less deadly.  

Thermodox

This article explains why thermodox could be very useful for liver cancer and metastasis:
http://seekingalpha.com/article/607921-celsion-is-ripe-for-a-long-position

Thermodox is a heat-activated form of doxurubin.    Combining thermodox with hyperthermia/RFA treatment could help deliver doxurubicin at higher concentration into liver metastasis (possibly kidney, pancreas)  locally.   As a result, side effect to heart is minimized while cancer gets its full of this powerful drug.

"Studies in a rabbit tumor model also showed that heat-activated ThermoDox delivered 10-fold more doxorubicin to the tumor, than conventional injections of doxorubicin. And although ThermoDox did accumulate to high levels in the kidney and spleen, it was not higher than conventional injections of doxorubicin. Finally, the 2008 Phase 1 trial for ThermoDox in liver cancer showed that an optimal dose of 50mg/m² extended the time-to-progression from 1 month to 6 months and, very importantly, the "dead zone" within the tumor kept expanding for 3 months after the radiofrequency ablation treatment, suggesting that heat-activated ThermoDox was killing the presumed chemo-resistant tumor cells with long-lasting effect. In contrast, the "dead zone" shrunk over time with radiofrequency ablation treatment alone. "

Metastasis: Rude Awakening

2 great articles on nature.com. The first, "Metastasis, Rude Awakening" highlighted the tragic lack of progress on MBC treatment plus problem of long term relapse from hidden metastasis:
http://www.nature.com/nature/journal/v485/n7400_supp/full/485S55a.html#/ref 7

nature.com is not the most popular science magazine in america.   If even nature.com readers need a "rude awakening",  metastatic breast cancer patients have a real problem.   The public, including early breast cancer patients and other well educated people who should know better, have been lulled into a false sense of security and think metastatic breast cancer is a "chronic" disease like diabetes or AIDS.   When in fact, MBC patients life expectancy is measured in years, even months, while diabetes/AIDS patient can expect a normal life expectancy, which is 70-80 years old.

The other article explained why current clinical trial design fails so many potentially good drugs, and how clinical trial process itself should be changed:
http://www.nature.com/nature/journal/v485/n7400_supp/full/485S58a.html


Different clinical trials should be conducted, with different end-point. The ultimate goal is to make the turn-around-time fast. So scientists can try a drug, wait a few days/weeks for results; tweak it to improve it, wait a few days/weeks for results; repeat above.

Currently the scientists must wait years and years for results every single human related iteration of drug design. No wonder effective treatments are few and far in between and very very expensive.   

Imagine one day there is a CTC test similar to blood glucose test, where patients can poke their fingers in morning/lunch/dinner time and get 3 data points.    Patients/physicians can see in real time how CTC is changing with new treatment/exercise regimen, and this data can be used to forecast patients' real response to medication and used in clinical trials, which takes a few months to run, instead of years and years.    Patients need not put their lives on the line to join a randomized clinical trial.  And 100% advanced breast cancer patients can join a clinical trial that generate a valid data point without having to make a commitment for years till death (for the OS benefit) .  Then we can say truly, that MBC is a chronic disease, like diabetes.  And its cure would not be far off.