Friday, February 27, 2015


Roy, Richard and Linda at the beach, 1947
I wish I had known Roy
Wow!  That’s all I can say: Wow!  The research team of J & R Ingwall has sent me a link to an article in the NY Times on a development in cancer therapy that gives promise of being a genuine breakthrough.  I urge you all to read it; it will certainly be on the next test.
Traditionally, cancer therapy has been specific to the affected organ: if you have ovarian cancer, for instance, you get one kind of drug, if you have prostate cancer you get another, and so forth.  Lately it has become recognized that organ-specific treatment may not be maximally effective, because – with many cancers – a single organ may have multiple “varieties” of tumor.  With ovarian there are four, I believe, which vary in their response to the traditional therapeutic protocol. 
However, we have known for a long time that cancer ultimately is the result of one or more mutations.  The new research described here looks at the mutations, not to where the tumor happens to reside.  For instance, a drug already in use for melanoma absolutely cured an elderly woman of Langerhans disease, which is a rare cancer of the white blood cells.  It appears that Langerhans disease (in this case, at least) is caused by the same mutation that in other people results in melanoma.  It was possible to determine that this is the case because sequencing of genes known to be involved in cancer has dropped in price from the high thousands to the low hundreds.  (Of dollars, obviously, although the same would be true nowadays if we were speaking in euros, thanks to the strong dollar.  Time to take that trip to Europe.)
The FDA seems gratifyingly cooperative for once.  Instead of insisting on a traditional trial, involving many hundreds of subjects, double-blindness with a control group, heaps of money and years of time,  they will simply look at the data (from smaller, less controlled studies) and ask the question:  “Is the American population better off with this drug than without it?”  Eminently sensible, for once.
So, the ongoing research goes something like this:  Oncologists from around the country will send tumor samples to various central labs, where the mutated gene(s) are determined.  The patient then is assigned to a “basket”, which “contains” all those with a tumor caused by that particular mutation, regardless of where the tumor may reside.  All patients in this basket will receive the same treatment set, and the results are scrutinized.  Marked improvement without severe complications will be taken as affirmation that the drug/treatment is efficacious.  The program under which this is being done is called “Match”, and is funded by NCI.  To me, this makes good sense.   I take back all the bad things I have written in the past about both FDA and NCI.  Well, some of them. 
As an example of what is possible, consider the “basket” that contained Mrs. Hurwitz, the lady with Langerhans disease.  Of the 70 individuals in her basket, 18 had one of two rare blood cancers.   Fourteen of these are cured, and the remaining four have only just started the treatment.
Of course, failures also have occurred.  One of them is described in the article:

Wednesday, February 25, 2015

ALL OVARIAN CANCER IS BAD: This kind is worst.

In Norway
I think that's a quilt shop in the background
Monday I was stranded in Flagstaff, AZ, in a snowstorm, with temperatures in the 20s or worse.  Today I am in Borrego Springs, wearing shorts.  What a difference a few thousand feet of elevation can make!  Not to mention a few  degrees of latitude (and maybe a nearby lake); I have been reluctant to contact Linda’s brother Dick, in Kalamazoo, MI, because I am jealous that he is getting all that exercise, shoveling snow, and I am not.   But, anyway…..
An important paper on ovarian cancer, judging by its press treatment, has just been released.  No fewer than three press articles covering the same topic were coughed up for me by Google Alerts; I will give you the links, below.  The work was done at Cambridge University, in England.  The methodology is beyond us, but the result seems to be that in OVCA, the more “heterogeneous”, the worse.  That is, the faster the cancer cells divide and mutate, the harder it is to kill them all at a single crack.  A particular chemo treatment may get most of the cancer cells, but if the damned thing is heterogeneous enough it always leaves a few that are resistant, free to grow and cause a relapse.  I think we already knew that, but at least this study has learned something about how the process operates.  I guess that’s helpful.
Here are the links.  They tend to be tough sledding.

Monday, February 16, 2015


Linda in Windsor Castle
Protected by Gurkas
The Queen was not at home

“If we understand it, we can fix it.”
With those words, Dr. Robert Eisenman of Fred Hutch reinforces my firm belief that continued work on the basic biology of cancer is valuable and ought to be richly and intelligently supported.
Dr. Eisenman works on the potential oncogene Myc.  Faithful readers will recognize this biological object; I have written about it several times before.  I still don’t understand what it does, but it is clear that – when mutated – it is implicit in cancer growth.  You can’t go after Myc directly, for several reasons, but apparently you can go after a protein called MondoA which mutated Myc needs to do its job in cancer – which is, to create material for cell growth.  MondoA is not necessary to healthy cells, it seems, so it is a fine target for an anti-cancer drug.  The Hutch people apparently already have located such drugs (orphan drugs?) and tested them on mice, successfully.  Unfortunately, “the human impact of these findings are years away”.  Again, an excess of caution – in my view.
Here is the article.  It is only one page long, so read it.

I have tangled with Myc several times, most notably on 7/2/12 and 10/3/12.  As you will see,Myc won on each occasion.

Wednesday, February 11, 2015


Linda on a Thames bridge
Her back is toward Windsor castle.
She looks forward toward Eton College, where the battle of Waterloo was won.
As many of you know, I am currently in Borrego Springs, CA.  Borrego Springs is located in the middle of a vast park, the Anza Borrego Desert State Park.  Our state park is the largest in the United States, beating out South Dakota’s Custer State Park by the area of one buffalo wallow.  Custer is famous for bison; we are famous for fossils (including fossil bison).  Most of my social life here in B.S. stems from participation in the ABDSP Paleontology Society.  We are a more-or-less dedicated group of more-or-less enthusiastic amateurs, who help the Park find, retrieve, clean up and repair, classify, and catalog – old bones and such things, which range in age back some 20 million years.    I joined the group ten or so years ago, chiefly because I enjoyed the field work – hiking all over the desert, looking for fossils.    But that was awhile back.  Now I have the energy and strength of a louse, as well as a balance problem that prevents me from clambering around over rough terrain.  I can still work in the lab and, of course, give geology lectures, but – let’s face it, I am a determent in the field.  Phooey!
Why am I telling you this?  Well, the main reason is to have something to do until the evening news comes on and I can have my vodka and grapefruit- juice cocktail.    But, also, I experienced an epiphany yesterday.  I went out with a dozen or so fellow enthusiasts to survey a bleak and seldom-visited place called June Wash.  It didn’t take me long to realize that I was a net loss to the group.  Vastly too much energy was expended in making sure the old man didn’t kill himself.  We found almost nothing.  Who knows: if the group had been looking for fossils instead of making sure I was still alive, maybe we would have found the Park’s first mastodon?  Why should you care?  Because I have officially renounced field work.  Instead, I intend to write more blogs, and cram even more cancer biology down your throats.  That’s why.
Okay, time for Lester Holt*.  Heavy biology ahead tomorrow.
Now is tomorrow, and you are going to be fascinated by the following biological concepts:         
   Immune checkpoint proteins and their inhibitors.
   Cytotoxic T lymphocytes, sometimes known as Killer T cells.
   Tumor-infiltrating myeloid cells.         
(And if you quit reading here, you are a wimp.)
This blog was stimulated by an article – “Compugen Presents New Results Supporting CGEN-15049 as Potential Cancer Immunotherapy Target” - published in an Israeli business journal which reports on a presentation at a cancer conference in Banff, Canada.  I didn’t understand it.  However, mining the internet for several hours brought me this far along the path to understanding:
The natural immune system consists of various cells, including Killer T-cells, the task of which is to patrol the body and destroy (“lyse”) any cell it finds there that doesn’t belong.  These beat cops of the bloodstream do not “lyse” normal cells, because these benign cells are covered with something called a checkpoint protein, whereas nasty invading cells are bare of such defenses.  Maliciously, cancer cells also can sport these proteins, which are called “checkpoints”, for some reason.  A very important checkpoint protein is called PD-L1, poetically termed the Programmed Death Ligand 1.  If you are an innocent little liver cell, for instance, that finds itself without a coating of PD-L1, you are toast: the immune system will devour you.  Cancers have plenty of external markers that identify them as something that ought to be devoured, but they also can produce a plethora of checkpoint proteins that deceive the immune cops and thus allow the cancer cell to avoid death.  Checkpoint inhibitors are designed to reduce the abundance of these checkpoint proteins, thus allowing the cancer cell to be identified, and eaten, by such things as our Killer T Cells.   
 And what of tumor-infiltrating myeloid cells?  Well, the correct answer to that question is, damned if I know.  Myeloid cells are essential to the production of blood, and these tumor-infiltrating things are needed for “angiogenesis”, which refers to the construction of blood vessels throughout the tumor.  Kill the myeloid cells and the tumor dies a horrible death – I guess.  So maybe these checkpoint inhibitors do a number on the myeloid cells, too.
At several places in all these articles I ran on the observation that, although these inhibitor-based therapies help, they are not a cure.   The thrust of research now seems to be, why?  Also, can we fix that?
But to end optimistically:  Here is a quotation from the article I will attempt to send you to:  With genetic sampling of individual cancers, in the future (around 2025) a patient may be able to get custom-crafted combinations of therapies that rapidly and totally eliminates any particular cancer.” As I said in an earlier blog: make it so.

Easy reading:

*  I like Lester, but I wish it were Brian.  Oh, Lord - what a screw-up!


Saturday, February 7, 2015


A somewhat peculiar picture of Linda and me
Where?  When?

“It is, Sir, as I have said, a small college.  Yet there are those who love it!”
This was Daniel Webster, commenting on Dartmouth College.
Well, I’m no Daniel Webster, that’s for sure – and I have never even visited Dartmouth College – but I could learn to love the place.  That is because of some promising research going on at that institution regarding the use of immune reactions to stifle ovarian cancer.  The following may not make sense, but here goes anyway:  Although I understand only the tiniest fraction of what these guys have done, I am encouraged just the same.
I tried, God knows I tried.  I read the news release.  I used Google Scholar, located the article, and read the abstract.   I tried to access the entire article (to look at the figures), but I was told “access denied”.  So, hell, here is what, in my blinding ignorance, I think is going on.
These guys are working with mice, in which they (inhumanely, but necessarily) have planted ovarian cancer.  They insert “an attenuated and safe” strain of a certain bacteria (Listeria monocytogenes, if you must know) into the little beasts.  This somehow changes the “tumor microenvironment” in such a way as to induce “immunosuppressive cells” to cease protecting the tumor, and instead go for its jugular.  There is much discussion of cytokines and chemokines. These are small signaling proteins that are important in the immune system, and elsewhere; if you want to know more, go to Google, like I did.  Apparently this kind of therapy is being tested on pancreatic cancer, as well as ovarian.
A quote may help:  “Now that we can engineer microorganisms to make them safe to use and also can track anti-tumor immune response in great detail, it has new potential for use in cancer treatment”.  As heard in Star Trek:  “Make it so!”
 And that, Dearly Beloved (to quote Kipling this time), is as far as I am going with this. 
Oh, here is the title of the article.  See how many words you recognize.  Attenuated Listeria monocytogenes reprograms M2-polarized tumor-associated macrophages in ovarian cancer leading to iNOS-mediated tumor cell lysis.
Finally, my hits counter informs me that nobody read any of my blogs yesterday, and nobody has read any so far today, either.  You don’t want to hurt my feelings, do you?

Tuesday, February 3, 2015


Linda, on top of the world.
Mt. Baker in the far background
Clicking on that will bring you, as if by magic, to the first time I stumbled over the concept of telomeres and telomerase.  If you read that blog you will instantly know as much about these important things as I do, and maybe more.  I mention this because the article I am about to describe arose from pure biological research into –  telomeres, of course.
The work was done at NYU, with contributions from several other places.  Apparently it began as pure curiosity-driven biology; the question: how do cells prevent telomeric ends of chromosomes from sticking together.  Part of the answer appears to be the existence of an enzyme – newly discovered? – called polymerase theta (abbreviated PolQ, for some reason.)  “Inhibiting” the action of this  stuff “dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 mutations.”  I think the remainder of the article attempts to explain why, or how - but I'm not sure.  There is a lot of science that I don’t understand tucked into this short article.  For me, the take-aways are rather simple:
Not a cure, but helpful nonetheless.  Long remissions are good.
Time and money spent on pure cellular biology are useful, and are to be encouraged.
Here it is.  Somebody explain it to me.

Friday, January 30, 2015


Linda and a grand nephew, Heron Island, Maine

As you probably know already, I have arranged for Google to alert me whenever an article concerning ovarian cancer appears in the world media.  Well, appears in English, I guess – nothing in Lithuanian so far.  .  Many of the articles they cough up are inconsequential, and a few are downright stupid.  However, some useful references also emerge.  As an example of the former, the Mirror (a U.K. tabloid – possibly the one that prints a full-page nude female on page three of every issue) reports that fizzy drinks cause cancer.  What they mean is that: (1) drinking an improbable amount of fizzy, sugary fluid causes puberty in girls to come a month or two early, and (2) early puberty increases the chances of developing certain kinds of cancer, especially breast and ovarian.  So, I guess our lesson here is to avoid fizzy drinks – mainly because they are disgusting in taste, make you fat, and rot your teeth.  Fear of cancer would appear to be fairly low on the list of reasons.
As an example of a useful article, the American Society of Clinical Oncology refers you to the following report:
This is something like an annual report of what ASCO regards as important advances in cancer research.  I can’t pretend that this is “I just couldn’t put it down” literature, but it has some interesting sections.   As you probably could have guessed, it contains an anguished plea for more Federal funding – the claim is made that the purchasing power of the cancer research community has decreased by 29% in the past decade.  No word about rearranging the way the available funds are distributed, of course – ASCO is cancer establishment, bigtime.  I, too, am unhappy when cancer funding is cut, but I continue to argue that the funds could be put to far more effective use:  see the following fascinating little essay
which you should re-read.  I’m sure my email buddy Clifton Leaf would agree.
In passing: a large percentage of “serious” articles that Google dredges up for me concern research that demonstrates that certain genetic mutations are related to certain kinds of cancer.  I guess such discoveries are cause for jubilation – or at least, a fleeting, grim little smile.  Clearly, simply knowing what aids and abets cancer-acquisition is of little value so long as we don’t know what to do about it.   So, your genomic investigation tells me that my daughter is carrying a mutation that may cause ovarian cancer.  So, what then?  Can we fix the mutation?  Can we reverse its malign effect?  That’s what I really want to know.  What am I paying your salary for, anyway?  Come on guys – get cracking
**I should warn you that opening this site may result in an obnoxious add – on my machine it does about half the time.  However, just close the add and the meat of the article will appears.