POTENTIALLY A REALLY BIG DEAL

Linda a long time ago

Okay, to optimally appreciate this blurb, you may need  to be reminded of the meaning of three terms

:

                Sensitivity:  The ability of a test to detect a medical condition, expressed as a percentage.

 

                Specificity: The ability of a test to determine that the condition does not exist, also a percentage.

OS:  Overall survival:  The fraction of people still alive at some time in the future,usually measured from time of diagnosis.

So, if the sensitivity of a test is 90%, it follows that 10% of the patients identified by the test will be “false positives”.  The rest have the disease.  Similarly, a specificity of 90% indicates that the test missed 10% 0f the patients who have the disease.  These are called “false negatives”.  Clearly, the higher the better, on both scores.  Tests with sensitivities and specificities of 50% or less probably aren’t worth doing.

Note that OS (overall survival) depends partly on how early a condition is detected.  If a condition is completely incurable, earlier detection will increase OS without affection the ultimate outcome at all.

So, here is a new blood-based cancer test that shows great promise.  Read about it.

https://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Bbbeb6c86-8bfd-4f41-9f51-b8ee577d7739%7D/novel-blood-test-aims-to-detect-cancer-in-its-earliest-stages

Since most of you WON’T read about it, here are some highlights.

The primary author is Joshua Cohen, from Johns Hopkins University (he has 41 co-authors, from almost as many labs!).  This mass of research talent has designed a blood-based assay that looks at 16 genes (you recall that cancers will shed fragments into the blood stream, right?) as well as eight proteins known to be associated with various cancers (CA-125, for instance).  Then, in a happy marriage of biology and computer science they used something called “supervised machine learning” to evaluate and extend the usefulness of their predictive algorithm, which they call cancerSEEK.  Input data came from 1005 patients known to have cancer from clinical evaluation.  The cancers screened for were ovarian, liver, stomach, breast, esophagus, lung, pancreas, and colorectal.  Median sensitivity across the board was 70% (98% for ovarian!), and overall specificity was 98%.  This, boys and girls, is damned good news!  But, inevitably – much more work needs to be done.  Five to ten years, says Dr. Cohen.

This paper appeared in Science – which validates my opinion that this is a big deal.  If you want to study the original paper, for a PDF click on

https://www.breastcarenetwork.com/wp-content/uploads/2018/01/Cohen-et-al-Science.pdf

In the PDF the authors estimate the cost of a cancerSEEK  run at $500.  That’s a lot, if applied to the entire population systematically and repeatedly.  Almost surely advancing technology will bring the price down, at least a little.  And, if we were able to stop building aircraft carriers and nuclear missiles, maybe we could swing it.  Let us fervently hope so.

POT TO THE RESCUE?

Linda lived in San Francisco in the '70s, but never smoked pot.

Yeah, sure.

We all know that there is a medicinal use for marijuana; to combat pain.  But I didn’t know that the organic ingredients with unpronounceable names found in pot may have cancer-fighting properties as well.  Did you?  Well, recent work by some graduate students  at the University College of Pharmacy in Kentucky indicates that extract of hemp (no marijuana in Kentucky, boy!) slows the growth of ovarian cancer cells.  Apparently it inhibits the health and vitality of the Interleukin family of organic molecules.  Interleukins enhance inflammation, and thereby facilitate cancer growth.  Or so it seems.  Progress, I guess.

By the way, this research utilized only the best Kentucky-grown hemp.  They want you to know that.

https://www.sciencedaily.com/releases/2018/04/180423155046.htm

OF MICE, NUDE MICE, AND NANOTUBES

Our Fur-less Friends

Well, the poor devil on the left

Do you know what an athymic nude mouse is?  Well, it is a hairless mouse with no thymus, abundantly used in cancer research.  Seems it lacks killer T cells, hence cannot resist the transplantation of various human cancers.  By God, we owe an enormous debt of gratitude to mice!  When we finally do conquer cancer, we should build a monument on The Mall.  The principal occupant should be the person (or computer algorithm) that finally cracked the conundrum – but crouching at his/her/its feet should be a marble mouse!

Which brings me to the subject of this blog.  As you know, detecting OVCA early enough to snuff it out is difficult.  Hell, to all intents and purposes, it’s impossible.  Now comes along a group who have constructed a carbon nanotube which has the characteristic of changing its electromagnetic  properties in the presence of the protein  HE4.  As demonstrated by the Fred Hutch group I used to help, high concentrations of HE4 are a “tell” for OVCA.  Unfortunately, by the time HR4 concentrations in blood samples reach a detectable level the patient is in stage 3.  These miraculous nanotubes, if located near the fallopian tubes, can do much better – or so indicate the nude mice. 

So, good, I guess.  But before I get too excited, I’d like to know:

                How do you implant the damned thing?

                Will every female baby get “implanted” at, say, birth?

                How often will a woman have to be “monitored?

                And, obviously – how much will it cost?

http://advances.sciencemag.org/content/4/4/eaaq1090

DYING

Guess Where

Here is a thoughtful, and thought-provoking, piece about miracle cures, palliative care, and the physician’s dilemma.  Read it.

https://www.nytimes.com/2018/04/19/opinion/sunday/problem-miracle-cancer-cures.html

My impressions:  It used to be a simple, if painful, matter for a doctor tending a dying cancer patient to tell the truth – we have exhausted all therapies, you are going to die, so consider palliative care.  Now, however, with immunotherapy and personalized medicine available (albeit at tremendous cost), the matter is far less clear-cut.  Such is our ferocious desire to live that even people in their 80s will choose to fight on, even though (says the article), only about 15% of patients will respond – and we don’t know who they are.  And, of course, side-effects may be horrendous.

I will be 85 in a few weeks.  If I contract cancer, for God’s sake don’t let me try anything heroic.  I want to exit life with a smile on my face and a vodka in my hand!

PROFILES IN RESEARCH EXCELLENCE: Dr. Pamela Kreeger

The Kreeger Lab

Well, not the lab, actually.  Just the people who work in it.

Insofar as it is possible, let me introduce Pamela K. Kreeger, Ph.D.  Dr. Kreeger graduated from Valparaiso University in 2000 (making her ~ 39 years old).  She received her Ph.D. from Northwestern University, post doc’d at M.I.T, and now is an Associate Professor at U. Wisconsin, Madison.  And that’s all I know about her personally, after 30 minutes of prying using the internet.  I could email her for more, but I won’t – I want her hard at work, not answering stupid questions from people like me.

Dr. Kreeger is affiliated with the Department of Bioengineering.  The lab has a newsletter:

https://www.kreegerlab.org/ 

which tells us that it (Pamela and co-authors) have published 27 studies in the last decade.  From the photo (above) she has nearly a dozen budding young scientists to supervise.  (In my prime I had as many as three, and expended much energy and wasted much time keeping them from killing each other.  I admire you, Pam).

Anyway, MRC has awarded Dr. Kreeger $60,000 to investigate the feasibility of using a drug already approved by the FDA (for other purposes) to inhibit metastasis in ovarian cancer.  It seems that this drug discourages cancer seeds carried in the blood stream from adhering to other parts of the abdomen.   Many mice will die to test whether this is true.  Let’s hope it is.  Thank you. Dr. Kreeger.

MRC

Scouting for Geronimo

Linda in Chiricahua National Monument

As many of you know, until a few years ago I volunteered with the Marsha Rivkin Center for Ovarian Cancer Research (hereafter MRC).  Gradually, however, my enthusiasm for MRC waned, and finally essentially disappeared.  This was owing to the fate of stuff I wrote for the MRC web site – it all vanished without a trace.  Now I find that I don’t know a single MRC staff member, except Saul  Rivkin himself – who has stopped phoning me, as he once did at least weekly.  Oh, well – Saul is getting old.  He’s almost as old as I am, in fact.  Practically antediluvian. 

But MRC still does good work.  It raises money and doles it out to young scientists who they think may be poised on the brink of an important discovery.  They have just announced their grantees for 2018; you can read about it here:

https://www.eurekalert.org/pub_releases/2018-04/g-trc041018.php

To demonstrate just how petty I can be, I would like to point out that even this press release contains an error.  Over 22 thousand American women contract OVCA yearly, not die from it.  The latter figure is more than 14 thousand – still an obscenely high number.

Anyway, MRC gives out four types of grant:

Pilot Studies:  These support investigations that are non-mainstream – innovative for sure, and perhaps a bit speculative.  In my not-particularly humble opinion, this is where the bulk of MRC money should go.  This year they awarded eleven Pilot Study grants, of $75 K each.

Scientific Scholar awards:  These also appear to be innovative.  Three were awarded this year, at $60 K per.  These seem to be aimed at extremely early-career investigators because grant applicants are required to designate a “mentor”.

Bridging Funding Awards:  Sad but true:  Not all worthy research ideas get funded by NIH or other governmental funding agencies.  Bridging Gtants - $30,000 for up to six months – give the proposer sustenance and encouragement to try again.  Two were awarded this year.

Challenge Grants:  This is a rather funky idea: propose a “grand scientific question to the scientific community”, then award $150,000 to the most promising proposal.  I don’t know what the “grand question” was this year, but – whatever it was – nobody got funded.

MRC, as frustrating as it is, serves one truly vital purpose:  it spurs innovation.  Breakthroughs rarely originate out of old, established research projects – and these, by the way, suck almost all of the oxygen out of available, mainstream, funding sources.  MRC and like organizations enable new ideas to be hatched and incubated.  If the new idea proves to be viable, the likes of Jeff Bezos or Mark Zuckerberg – or even NIH - can step in and do the heavy fiscal lifting.  But first the idea must exist.

  

So, go get ‘em, MRC.  My next blog will be another in my series “Profiles in Research Excellence”, chosen from your 2018 awardees.  Her name is Pamela.  

AN ANTI-CANCER VACCINE? Nope, not yet

         X-Country skiing, in Canada

According to Google this is the 574^th blog entry I have inflicted on you since March of 2012.  In other words, I have been writing these things for over six years, at a rate of about 95 per year.  I hope they have done some good.  Lately, however, I have begun to realize that I am growing non-selective, and repetitious.  For instance, I have written about immunotherapy 38 times, over a span of nearly six years.  What happens is that my sources often make the new process or discovery they are discussing sound like sliced bread, Teflon, or the internet – real society-shaking breakthroughs.  But in general they aren’t.  My tendency is to get all excited, and blog away.  No more, by golly!  From now on I intend to write only about  such things as strike me as certainly significant, useful compilations of information – or just plain interesting.

Partly I am doing this because I can’t keep up with my daily deluge of emailed information.  For instance, somewhere in the last few days I skimmed an interesting blurb about the new FDA director, who is endeavoring to speed up the drug-approval process.  A worthy ambition, certainly – but I have totally lost the article.  Anyway, it appears that we don’t have to hate the Feds quite so much now, at least for the time being.

For something useful to end this blog:  An outfit called Taplmmune, based in Jacksonville, predicts that by 2022 they will have perfected a “vaccine” against OVCA.  This on the basis of a Phase I trial involving ten women with ovarian cancer!  To me, a vaccine is something you somehow ingest in order to avoid getting a disease.  This stuff, with luck, may give a woman six extra months of remission.  I don’t deny the value of another half-year of healthy life; I would have given anything to have had Linda alive and happy an extra  six months.  So Taplmmune’s new concoction may be useful  - but a vaccine it ain’t.

http://news.wjct.org/post/jacksonville-based-company-says-new-cancer-vaccine-could-be-available-2022

SYNERGY

Linda and Mitzi take a nap

I like to think that I have a pretty good vocabulary.  When I was a kid my parents subscribed to Reader’s Digest, which often featured a section called “It Pays to Increase your Word Power”.  This consisted of 20 unusual words, each with multiple possible meanings – you were supposed to pick the right ones.  I used to compete at that with my dad; he usually won, but I hung close.

So, even today, I wince whenever I run on a word usage that is unfamiliar.  I ran on two such just now.  The first is “synergy”.  I know what it means – roughly, two or more things working together that produce a result greater than the sum of the individual contributions – but I have to stop and think about it.  The other is “inform”.  To me, to “inform” is to squeal on your class mate who has been firing spit-balls at the back of the teacher’s neck.  However, it also can refer to facts bolstering a proposition, as “the laws of physics inform the proposition that, if I turn suddenly and bump this coffee cup with my elbow it will spill all over the floor.”

Well, the article recommended (below) use both of those words, plus a few medical terms that might be unfamiliar.  It concerns a bright young man who has just received a handsome grant from the National Institutes of Health (NIH) to continue his study of the synergistic effect of employing low-intensity radiation together with an immunotherapy drug to combat cancer.  How it works is a bit of a mystery to your old blogmeister, but it may go something like this.  Irradiate a tumor with X-rays and you will kill a lot of its cells by disrupting their DNA.  Some will survive, however, but may react as if they have been invaded by a DNA virus, causing them to display on their surfaces a type of protein that hollers out “come and kill me” to the immune system – which responds appropriately.  There also is some synergistic effect involving things called Tregs, which I don’t understand.

All this is informed by previous research performed by this bright young man – his name is Zachary Morris, and he now is on the faculty of the University of Wisconsin. 

By the way:  I strongly recommend the NIH  Director’s Blog (which Google), from which this stuff was taken.  You can sign up for automatic delivery to your email account.   It only shows up once/week or so, so it won’t clutter your inbox.

https://directorsblog.nih.gov/2018/04/05/creative-minds-optimizing-radio-immunotherapy/

A HANDY SUMMARY FOR YOU HOT DOGS

Too much sun in our eyes

but a good shot, nonetheless

NCI has published an “infographic” that can serve as a Cliff Note for all you avid students of cancer and genetics.  Here it is:

https://visualsonline.cancer.gov/details.cfm?cid=eb_govdel&imageid=11950

I am sure that this will be useful, but I can’t claim that I recommend it after careful personal examination.  The text is fine, certainly – but the fancy diagram evades the acuity of my ancient eyes.  I tried to make a paper copy, but rather than respond properly my printer spit out an endless stream of nonsense about a Viking trip – which I couldn’t terminate – and finally stuffed a paper in crosswise, screamed, and shut off.  I can’t get it to try again.

We can build quantum computers and driver-less cars.  Why can’t we build printers that old farts like me can operate?