MORE ON CANCER STEM CELLS

Santorini, ~ 1984

Sometimes valuable information appears in unexpected places.  For instance, a significant percentage of Google Alerts on ovarian cancer cite Wall Street-type publications.  Think about it for a minute and you will quickly understand; cancer-treatment breakthroughs often lead to profit bonanzas for Big Pharma, or Little Pharma for that matter.  The alert investor must be ready to jump.

I mention this because of an article I just read that appeared in TheStreet.com.  It appears that scientists working for Verastem (presumably part of Little Pharma) have determined that chemotherapy actually stimulates the activity of cancer stem cells.  This, it seems to me, is a significant setback.

You know how it goes.  Woman diagnosed with OVCA undergoes debulking surgery, followed by adjuvant chemo.  Remission ensues.  However, some months or years later the cancer returns.  Five-year survival rate is <50%.  What are increasingly termed cancer stem cells are to blame.

Research performed by the Verastem people suggests that, far from wiping out the CSC, chemo actually invigorates them!  This is said to follow from a trial comparing length of remission in women who had surgery plus chemo with the same for women who had only surgery.  The latter lived longer.  Well, that’s not certain; what was actually observed was a large increase in unhealthy mutations in the surgery plus chemo group.  Experiments with mice also showed that chemo was counter-productive.

So, what to say?

What are these freaking CSCs, anyway, and why can’t we confront them directly?

How many onco-docs would be willing to forego adjuvant therapy?  Damned few, I would guess.

Will Verastem succeed in ongoing efforts to develop drugs that can kill CSC?  And if so……………….

How can we buy its stock?

Here is the article:  http://www.streetinsider.com/Corporate+News/Verastem+(VSTM)+Presents+Data+on+Supporting+Preferential+Targeting+of+Ovarian+Cancer+Stem+Cells/11441037.html

And here is an old blog on CSC:  http://ljb-quiltcutie.blogspot.com/2012/08/cancer-stem-cells-may-they-rot-int-hell.html

OVARIAN CYSTS: So, you would rather talk baseball?

With a Hunsinger kid, on an expedition

Ovarian cysts sometimes develop into ovarian cancer, and that is why I bring this article to your attention.  Half the world’s population should be interested; the other half (my half) would prefer to be spared the gory details.

http://www.livescience.com/54135-ovarian-cysts.html

Seriously, this article is packed with important information.



NCI brings you NIR-PIT

Bliss

I have commented before about the total dependency of the medical profession on acronyms.  This is understandable; if someone writing a paper wanted to discuss naphthalocyaninetrimethylphosphate, for instance  and had to spell it out every time it came up, the paper would be too long to publish, and if published would be impossible to read without coffee and naps.  So:

NCI = National Cancer Institute

NIR = Near Infrared

PIT = Photo Immunotherapy

Treg =Regulatory T cells

This* article from the NCI Newsletter describes another neat trick employing light to activate cancer suppressing agents.  To jog your memory, using light as a weapon against cancer came up earlier:

http://ljb-quiltcutie.blogspot.com/2015/08/more-light-on-cancer.html.  I was encouraged then, and am more so now.

If I understand the NCI article, the new wrinkle goes something like this:  There are two parts.

First, some guys at NCI have succeeded in attaching a “photo-absorber”  to  an antibody specific to receptors  that are “over expressed” on a certain kind of cancer cell.  Then, when the antibody is firmly attached, the appropriate near-infrared light is turned on, the photo receptor swells and the cancer cell is blown all to hell.  Better yet, fragments of the cancer cell in the bloodstream are recognized as “invaders”, triggering an immune response, causing killer T cells to course through the body, looking for similar cancer cells to kill.  Or something like that.  The catch here is that it is necessary to gin up a separate antibody for each cancer type.

However, there seems to be a more general approach.  If I am not too far afield here, the article seems to be saying that in the cancer’s “microenvironment” there exist immune cells (Tregs) that prevent the killer T cells from doing their job.  The game, then, is to attach the light-sensitive photo-bombs to molecules that bind to Tregs – and blow them all to hell.  All cancers have the same kind of Treg, so it seems as though there are the glimmerings of a powerful weapon here.  I am puzzled ,though, about whether it would be necessary to target T cells to each distinct cancer type.  I am over my head here, and had better stop,

By the way, don't hold your breath - phase 2 trials are just beginning..

·    *   http://www.cancer.gov/news-events/cancer-currents-blog/2016/photoimmunotherapy-cancer?cid=eb_govdel  

LIES, DAMNED LIES, AND CANCER STATISTICS

Nice picture

In the “War on Cancer”, who is winning – cancer, or us?  Experts disagree; for instance, Vincent DeVita says we humans are winning

 (http://ljb-quiltcutie.blogspot.com/2016/03/warts-and-all.html)

 whereas Clifton Leak puts his money on cancer

 (http://ljb-quiltcutie.blogspot.com/2014/06/the-truth-in-small-doses-at-long-last_7.html)

 Me, I’m on the fence.  By and large we are inching ahead, but in some areas progress occurs in millimeters, not miles.  In a way this “War” reminds me of WW1 trench warfare; incredible quantities of resources expended, with little gain.

After all, we should be winning, right?  The enemy here is brute biology, driven by natural law.  It’s not as if Napoleon is lurking behind the line, plotting to do us in.  If we are losing it’s because we are doing some things wrong.  Some things we can’t prevent of course – aging, for instance, but others we can – sunscreen, fiber, boring diets leap to mind.  So cancer incidence and mortality should decrease and, by and large they do – but at a pitiful rate.

This by way of introducing the NCI Annual Report on the Status of Cancer, which you can read here

:

(http://www.cancer.gov/research/progress/annual-report-nation)

The report covers two areas: changes per year (2003-2012) in incidence (getting it) and mortality (dying from it).  For men, incidence is down (1.4)%, whereas for women there was no change.  Thyroid and liver cancer incidence in both groups were sharply up (>5%).  Ovarian cancer incidence declined minutely (0.9%).

The mortality graph is similar.  These figures are for 10 year mortality, so don’t swallow them whole.  Ten year mortality asks “was the patient alive 10 years after diagnosis?”  This means that if you were diagnosed in 1995 and were still alive in 2005, you go in the plus column – even if you die the next year.  As earlier diagnosis becomes feasible, this sort of “survival” statistic is bound to improve.  But, for what it’s worth: overall survival improved by 1.8%/year for men, and 1.6%/year for women.  Again, ovarian cancer survival improved a bit: 2.0%.

The report concludes with an interesting discussion of liver cancer, which has spiked recently.  The reason seems to be the effect of the hepatitis C virus, as well as excess boozing.  Men are three times more likely than women to contract liver cancer, and there is a clear correlation between liver cancer and race: for instance, liver cancer is more than twice as prevalent among Native Americans as among Anglos.  Lots of room here for speculation.

SOMETHING NEW ABOUT CALCIUM

Many, many years ago.

Linda is disgruntled, Carolyn is content, and Eben is - well - engaged in an all-too-human activity.



I was pleased to encounter this article in Google alerts.  It not only contains some encouraging results, but it also gives me a chance to show of some of my (superficial) grasp of biology.

There are two kinds of cells: eukaryotic and prokaryotic.  (Yes, you knew that already.  Bear with me.)  Our friends the bacteria are composed of prokaryotic cells, whereas all we multi-celled organisms use the eukaryotic kind.  Eukaryotic cells are big and complicated.  In addition to a lot of goo called cytoplasm, they contain membrane-bound compartments known as organelles.  The nucleus is an organelle.  So are mitochondria. 

Mitochondria are the power-plants of cellular life, in that they convert “fuel” (food) into energy.  They do this by manufacturing something called adenosine triphosphate (ATP).  The mission in life of ATP seems to be to wander about slapping energy-rich phosphate groups on things that need to go.  Without ATP, we croak.

Incidentally, an interesting hypothesis holds that mitochondria once may have existed as independent  cells that were engulfed and enslaved by bigger cells.  Evidence for this includes the fact that mitochondria have their own DNA.  As the bigger cell protects the mitochondria, I guess this is a case of symbiosis.

Anyway, mitochondria communicate with the rest of the cell by means of a “messenger”; in this case, calcium ions (Ca2+).  Thus, if the cell needs more energy it releases Ca2+ ions from another organelle, the endoplasmic reticulum (ER).  Please do not ask me what THAT thing does.

So, it appears that some stuff found in sea sponges in effect blocks holes in the ER out of which the calcium ions are emitted.  Deprived of Ca2+ stimulus, the cell goes into “bioenergetics crises”.  In the case of normal cells, the crises can be mitigated by a process called autophagy, which translates into “self-eating” – and the cell can survive.  However, for some (not explained) reason – possibly because they divide so frequently – cancer cells die.  Or so say mouse-model studies, as well as studies using human cell lines.  Potential for useful cancer therapies are evident,

Here is the article:  http://www.cancer.gov/news-events/cancer-currents-blog/2016/blocking-calcium?cid=eb_govdel

By the way, I wish someone with some formal training in biology would explain to me what happens to the mitochondria when a eukaryotic cell undergoes mitosis.

  

VAMPIRE BLOOD

Linda and her cousin Elsie

Heron Island, Maine, 2008

 

I don’t really know what to say about this.  I stumbled on it by clicking on

http://www.dailystar.cw.uk/news/latest-news/508667/gran-Gail-Harling-cured-of-cancer-by-vampire-blood-injection-replacement-treatment

which turned up in a recent Google Alert.  In doing so I violated my invariant rule: never read anything printed in a British tabloid.  But how can you resist something with the title “Gran Gail “cured” of cancer by banned “vampire” blood treatment”? 

It appears that this youngish grandmother of seven was sent home to die, with advanced metastatic ovarian cancer.  She understandably was reluctant to do so, so in desperation subscribed to a service that supplies whole human blood for injection – at nearly $600 per pop.  This treatment is banned by the British health authorities as being unsafe and of unproven utility.  However, six years later Gran Gail is alive and cancer-free.  What to think?

Well, obviously – Hooray!  Anyone who beats ovarian cancer, by whatever means, is to be celebrated.  But how did it happen?  A list:

Maybe the docs screwed up and she never had OVCA.  Possible, but unlikely.

Maybe faith-healing kicked in bigtime.  That is, maybe Gail believed so fervently that ‘vampire’ blood would do the trick that her body somehow just kicked the cancer out.  Also unlikely, but stranger things have happened. 

Maybe the blood Gail received contained some organic molecule that somehow kick-started the immune system and caused it to turn on the cancer cells and kill them.  I hope this is the answer, but…

Maybe the Sunday Daily Star made the whole thing up, in order to fill out their front page.

One thing is certain, though.  We know an awful lot about cancer – but we still don’t know enough.

 

.

 

 



PROFILES IN RESEARCH EXCELLENCE: David Pepin, PhD

At a Maine clambake, about 2008





The Marsha Rivkin Center for Ovarian Cancer Research has released the names of their 2016 awardees, so it is time for me to extend my series of Profiles in Research Excellence.  I hope my choices appreciate being selected (there are ten of them now): not a promotion, not tenure, not more money, and precious little publicity – but maybe better than nothing.

There were three Scientific Scholar awards this year, and all of them sound promising.  I chose Dr. Pepin because his work involves something called Mullerian Inhibiting Substance (MIS), and for several years I have been running on references to this stuff and promising myself to look it up – and never have.  Thus, I reasoned, by selecting Dr. Pepin I would be forced to come to terms with MIS.  Well, as you might have guessed, I was very quickly in over my head.  Here is what I know, or think I know.

Mullerian tubes were first described by a German scientist of the 19^th century, named – of course – Muller.  They are present in embryos and, in females, develop into the uterus, etc.  In males they must be “suppressed”, and are thus bathed in a hormone called MIS.  So, what on earth does this have to do with ovarian cancer?

Well, very often initial chemotherapeutic treatment results in a deep remission which may last for many months, or even years.  However, all too frequently the cancer returns.  It appear that some cells – sometimes referred to as cancer stem cells – are resistant to chemo.  However, Pepin and his colleagues have given reason to believe that these stem cells will succumb to a stiff dose of MIS.  If they, too, are wiped out the cancer is, by God, cured!  How MIS does it work, and how Pepin’s group manage to beef it up to lethal levels, are of course beyond me.  If MIS therapy really works, and if it had been in existence 10 years ago, the lady at the top of the page might still be alive.

David Pepin, PhD, was originally educated in Canada.  He is now attached to Mass General (teaching hospital for Harvard), perhaps as a post doc.  He is working under the supervision of a well-known cancer doc, Patricia Donohoe.  From his picture he is young, bright-eyed and bubbling over with energy.  MRC gave him $60,000, and I am sure he will spend it well.

 

GLUMNESS GROWS

Mitzi, Linda, and Me

I hate it when I am right about things I don’t want to be right about! 

I have commented several times, quite glumly about how the “Moonshot” effort was likely to founder in a sea of bureaucracy, caution, reverence for hoary tradition, turf war, and an overall indifference to or fear of genuine innovation.  Call it swimming in the Sargasso Sea of government science.  Or maybe, just call it bucking NIH and the FDA.  Anyway, here are ominous signs and portents of stagnation and disaster.

Joe Biden, our VP is, as you know, charged with directing the Moonshot: our latest war on cancer; As you also know, Joe is a politician, not a scientist.  Naturally, he will need advice, - and BOY will he get it!

First off, he will receive input from something called the National Cancer Board (NCB).  This consists of 16 members, plus 12 ex officio members – not to mention an Executive Secretary with a Ph.D.  Clearly this is not sufficient to guide Joe, so the NCB itself will be assisted by the combined wisdom of the National Cancer Advisory Board (NCAB).  The NCAB is comprised of 28 individuals from as many institutions, all but a very few from the east coast.  There is a two-person overlap between the NCB and the NCAB, meaning that Joe will receive learned input from 42 individuals – if the 12 ex officious lay low.  See why I am glum?  

My glumness, largely rooted in a dread of bureaucracy, is augmented by the fact that, after reading cancer-related literature for four years, only three of these 42 folks have names that I recognize.  One is Beth Karlan, based in Los Angeles, who used to co-operate with my Hutch group when it was alive and functional.   She is good.  Another – natch – is the head of NIH.  I am cheered somewhat by being able to report that the NCAB also contains Dr. Patrick Soon-Shiong : elsewhere I have proposed Dr. S – S as a candidate for Cancer Czar.  TRhe signs are clear, though, that, nothing like this (Cancer Czardom) is likely to occur.

So, Joe:  Maybe you should have run for President after all.

Once again here is a summary of the Beck Blue-ribbon Committee on how to win the war on cancer:

Create a new agency to direct the battle.  Do not make it a part of NIH.  You can call it the National Cancer Institute (NCI), to fool budget hawks in Congress into believing that a new agency is not being created – but insure that it is profoundly reorganized.  Make sure that authority flows from the top down, not the other way around.

Appoint some hyperactive genius polymath as Head.  Call him (or her) whatever you like, but make sure it is a synonym of Cancer Czar.  .As stated above, Dr. S – S is the kind of guy we need, but no doubt there are other brilliant, ambitious, internally  driven masochists that would, and could, do the job.

.

Appoint an Advisory Committee of no more than a half-dozen top cancer scientists.  Replace them every two or three years.  Their duties should consist of:

                Thoughtfully answering any questions put to them by the Cancer Czar.

                Study the literature, think hard, and present ideas (respectfully) to the Cancer Czar.

                Review the efficacy of existing projects, and suggest modifications if needed.

                Help fight the old guard about how grant money is allocated, and spent.

And of course,then there’s Joe.  His duties would be to wage defensive warfare against the NIH and offensive warfare against Congress.  He also should be the smiling, confident, avuncular face of the War.  But, of course, he’s a politician so that sort of thing should come naturally.

Here are some links:

http://ljb-quiltcutie.blogspot.com/2014/12/the-richest-guy-in-la-and-also-most.html

http://ljb-quiltcutie.blogspot.com/2016/01/the-moonshot-part-e.html