Friday, April 1, 2011

Genetically Informed Medicine

I wish I was smart, astute, or quick enough to have developed the above phase, "genetically informed medicine." It captures part of the essence of my current medically-oriented research obsession. The article in which I read this was titled, The "Me Decade" of Cancer (see Reference #1). It's a play on the baby boomer "me" generation and covers the topics of personalized medicine and genetics. The phase used in the article was by Harold Varmus, Director of the National Cancer Institute (NCI).

There is a quiet revolution taking place in the world of genetically focused cancer treatment.
  • For those with Ovarian cancer, a non-profit, The Clearity Foundation, will help women create a molecular model of their tumor and based on the specific genetics of that tumor, they will recommend treatment options (see reference #2).
  • For those with Melanoma, another group, CancerCommons, has created a molecular model of melanoma and is offering treatment guidance based on one's genetic code (see reference #3).
  • There is even a molecular model for head and neck cancer (see reference #4). This too offers insight into potential genetic-driven treatment options.
I am not sure where all this will lead, but the future of individualize medicine is gaining momentum and appears bright.

Take care everyone.

References
==========
Ref #1 - The "Me Decade" of Cancer
http://www.the-scientist.com/article/display/58059/

Ref #2 - The Clearity Foundation
http://www.clearityfoundation.org/clearity-overview.aspx

Ref #3 - Cancer Commons
http://www.cancercommons.org/

Ref #4 - The Molecular Biology of Head & Neck Cancer
http://www.medscape.com/viewarticle/735920


Once again, I'd like to encourage a dialogue with those that find this information useful. It is easy to post a comment. Below is an image of a world map with pin points of recent blog visitors. Although many readers live in the US, this blog has gained a truly global following... India, Australia, Singapore, Egypt, Greece, Switzerland, Nigeria, and many other foreign lands.

You can double click on the map image to enlarge it.
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Tuesday, March 22, 2011

An “Ah-Ha” Moment for the Oncology Community

This is my third attempt at writing this complex blog entry. The first two attempts were too cumbersome and convoluted; they did however help me crystallize my viewpoint.

Here’s the hypothesis…

Given relatively recent advances in genetic testing, the human genome project, the cancer genome project, and human cell molecular modeling, individual results from clinical cancer trials are being sorely underutilized.

Personally, I’m closest to head and neck cancer as I follow news stories on it daily. However, my hypothesis applies to all clinical cancer trials. I will use a head and neck clinical cancer trial as an example in support of this hypothesis.

There are a set of head and neck oncologists who believe that patients with recurrent head and neck squamous cell carcinoma who do not respond to platinum-based chemotherapy have run out of treatment options and in turn have a very poor prognosis. See link in Reference #1 at the bottom of this blog entry. The article is about a paper presented at the 2010 ASCO (American Society of Clinical Oncologists) meeting and it backs up this assertion of a poor patient prognosis.

There have been early phase clinical head and neck cancer trials which on the surface have shown promising, but inconclusive results. See link in Reference #2 at the bottom of this blog entry to clinical trial NCT00442507 at www.clinicaltrials.gov. This was a phase II trial using a combination of Tarceva and Avastin that included 48 patients beginning in March 2007 and ending in January 2009. The results of that trial were printed in an article on www.cancerconnect.com (see Reference #3). On the surface the results of the clinical trial are positive, but lukewarm… Article headline, “Combination of Avastin® and Tarceva® Shows Promise in Head and Neck Cancer.” If you read the article it goes on to say, “Seven patients experienced a complete or partial disappearance of detectable cancer.”

Here’s the quandary. A group of oncologists at last year’s preeminent oncology event, ASCO, reported that the prognosis for recurrent head and neck cancer patients who failed platinum-based chemotherapy was poor. Yet, we have a study which completed in January 2009 where seven patients which fit the profile of this poor prognosis group experienced a complete or partial disappearance of detectable cancer. To my eyes, this is a major disconnect in viewpoints.

If, and this is a big “if,” one was able to use recently developed genetic testing to have pre-picked just those seven patients for this trial, the article headline would have read, “HEAD & NECK CANCER CURED IN SOME PATIENTS,” it would not be “Shows Promising Results.”

If I were part of the oncology community, this would be an “Ah-Ha” moment for me. What can we learn from those seven patients that will allow us to effectively use these targeted chemotherapies to save lives efficiently? I don’t know if the oncologists running this clinical trial have thought about exploring this path of reasoning. If my hypothesis is correct, they haven’t. In this example, I hope I'm wrong.

To test this hypothesis, I’m going to try and contact the oncologists for this clinical trial to understand where the results from this trial have led. Please remember, this is just one example. In a more strategic sense, what can we learn from all the other individual successes in all the other clinical cancer trials that have been recently completed or are in progress? My hypothesis says that the individual successes are being underutilized. More on this story as further facts are known.

Take care everyone.

References
==========
Ref #1 – 2010 ASCO Presentation article
http://www.medpagetoday.com/HematologyOncology/OtherCancers/25227

Ref #2 – Clinical Trial
http://clinicaltrials.gov/ct2/show/NCT00442507?term=head+neck+tarceva+avastin&rank=7

Ref #3 – Clinical Trial results article
http://news.cancerconnect.com/combination-of-avastin-and-tarceva-shows-promise-in-head-and-neck-cancer/

Post Script
==========
I struggled with this blog entry. Another appropriate title would be, "Reverse engineering a cure for cancer."
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Thursday, February 3, 2011

Genetics and Cancer Treatment

This blog entry is not about my cancer. It’s focused on how genetic research and findings are transforming the field of cancer treatment. The first part of this blog will provide a foundation by way of definitions and a few basic premises. The second part will cite an article in today’s WSJ about how genetic testing could improve the prognosis and ultimately the treatment of prostate cancer.

Definitions, Foundation, and Hypothesis
==================================



Cancer cells: Uncontrolled growth of aberant cells in the body. Cancer cells can grow, divide, and invade normal tissue in the body.

Gene: The basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring. There are approximately three billion genes in humans.

DNA (deoxyribonucleic acid): A long linear polymer found in the nucleus of a cell and formed from nucleotides and shaped like a double helix; associated with the transmission of genetic information

Chromosome: An organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. Humans have 22 chromosome pairs plus two sex chromosomes.

Genome: An understanding of the complete set of a living organism’s DNA.

Human Genome Project (HGP): An international scientific research project with a primary goal to determine the sequence of chemical base pairs which make up DNA and to identify and map the approximately 20,000–25,000 genes of the human genome from both a physical and functional standpoint.

Cancer Genome Project: Building off of the HGP and using high throughput mutation detection techniques, its goal is to identify somatically (i.e., cells in the human body) acquired sequence variants/mutations and hence identify genes critical in the development of human cancers.

Proteins serve many different functions within the chromosome and there are many different types of proteins. As such, I’m not going to define “protein” see (Wikipedia for a definition if interested). One function of a type of protein is cell division, either to encourage or discourage a cell from dividing. Proteins are complex and some proteins which regulate the growth of cancer cells have unique pathways. Admittedly, my knowledge here is weak and therefore should be treated as such. With this caveat, I’ll try to provide an example. In Head and Neck cancer, which for the most part is Squamous Cell Carcinoma, there is a protein called p53. This protein is also known as a tumor suppressor. There are other proteins which inactivate protein p53. Plus, to add to the complexity, the p53 protein may become compromised. So, in theory, if one could either 1) destroy the mutant p53 protein or 2) inactivate the proteins which inactivate the protein properly functioning p53 (yes, a double negative), then p53 could do its job in blocking the unregulated growth of cancer cells. From here, I’m on even thinner ice as I’m not sure about the relationship between p53 and my next statement (yet). Tarceva, a drug I have been on for 38 months is an EGFR (Epidural Growth Factor Receptor) inhibitor. It has special properties which in some way target a pathway into a protein which plays a significant role in solid cancer tumor growth. This is all very complex, so let me get to the hypothesis of this paragraph.

Hypothesis: If, through individualized genetic testing, one could find patients with an over-expression of the protein (or pathway) which Tarceva attacks, Tarceva (which is very expensive) could be targeted to those individuals for whom there is evidence of benefit (i.e., evidence based treatment). This in turn should increase the overall effectiveness of Tarceva on the population which is genetically receptive to this treatment regimen. It would in turn reduce unnecessary Tarceva treatment and reduce healthcare costs without impacting heath care effectiveness.

Today’s WSJ Article on Genetic Profiling and Cancer Treatment
============================================

You may have thought I forgot about part two of this blog entry. I found today’s (2/3/2011) news story in the WSJ titled, “New Clues to Treat Prostate Cancer,” fascinating. It is about how four genes play an intricate and interrelated role is predicting which individuals with prostate cancers have an aggressive cancer where treatment (e.g., radiation, surgery) is recommended versus one in which it should be watched without treatment.

Here are the article highlights. The findings so far is in mice, not man. Human testing is a few years off. One study cited in the article said that 48 men were treated with radiation or surgery to save one life. (Note, although this was not in the article, side effects from prostate treatment can include erectile dysfunction, incontinence, and surgical complications.) The article went on to say that if this genetic test could increase the odds of determining who should have treatment from our current standard of care test (an individual’s PSA level and biopsy) which predicts at a 60 – 70% to a 90% level that many men with a "favorable profile" might want to monitor the progress of their cancer for a while before deciding to undergo aggressive treatment.

To me, this is a game changer and yet another example of how our genetic understanding will impact medical practice over the coming years.

For those with access to the online version of the Wall Street Journal, here’s a link to the article…

http://online.wsj.com/article/SB10001424052748703960804576120194229203936.html?mod=djkeyword

Take care everyone.

Ed

Friday, January 7, 2011

Happy New Year... And, a Brief Health Update

Hi,

I had a Head & Neck CT scan and a follow up visit with my oncologist on January 5th. The radiology report was finalized today and all systems are clear. No new evidence of disease and my anatomy, when compared to my last CT scan in June, appears stable. So, all good news.

On the subject of improving my speech and swallowing functions (see background from December 2 2010 blog entry), the news is disappointing. I visited with my reconstructive surgeon and his physician assistant on January 3rd. It had been over three years since I had last seen him. We spent a very high quality hour together going over my options. I won't get into the detail here, they are just not that interesting to anyone but me. The bottom line was... make the best of what I have; surgical treatment is not a viable option due to the treatment risk of performing surgery in an irradiated area. In early December I was in touch with the UC Davis physician who did the implant on the head and neck cancer patient in Uruguay to help with his swallowing function. I may still schedule a consultation with him, but I have to be cautious. For me, even a minor surgery in an irradiated area may lead to long term disastrous complications.

Happy 2011. Stay healthy.

Ed

Monday, December 13, 2010

December 13 2010 – My Cancerversary

Hi Out There!

4 years ago today my doctor suggested palliative care as a treatment option. Well, I'm still here. Some days that surprises even me. I'm 3 years and 2 months with no evidence of disease (NED) and my current status as of last December moved from NED to "clinical remission."

My sister sent me a book in early December titled, "The Emperor of All Maladies." It is a biography of cancer written by a cancer physician and researcher at Columbia University. It was published last month and was named as one of the 10 best books of 2010 by the New York Times Book Review Magazine yesterday. This blog entry reflects on information covered in that book; it is not a book review, but more about what I took away from it.

The book crystallized a concern which has been nagging at me for some time. The concern is that I am not cured and never will be. Cancer is a series of cell aberrations; it is not just one aberrant cell event. That is why one might hear the term precancerous; it is a cell (or group of cells) which are heading toward becoming cancer, but haven't fully matured. Some precancerous cells never mature, others do. Triggers for moving cells from one stage to another are becoming better understood due to genetic and genome research, but a single cell can lie dormant for decades just waiting for its trigger.

Recent studies support the hypothesis that some cancers are caused by cancer stem cells. By eliminating the body of all known active cancer cells via treatment and entering into a state of remission, cancer stem cells can still remain in one’s body. These unaffected and remaining cells can begin producing new aberrant cells leading to a relapse at any time. This insight, as well as others, is changing the way researchers view the "war on cancer" from one of curing it to one of treating it as a life long chronic illness. Although I am in remission, for me, this war is far from over and I relive it frequently.

The book also reinforced hope for the future by providing a much deeper understanding into the world of targeted cancer drug therapies. I’ve been on Tarceva, a targeted chemotherapy drug, for over 3 years. Two new, potentially more effective, targeted therapy drugs are in the pipeline: OncoVEXGM (about to launch a phase III trial) and REOLYSIN (currently in a phase III trial). Both of these drugs are for head and neck cancer (note, these specific drugs were not mentioned in the book, but I’ve been following their progress elsewhere).

Without complaining (why me), I’ve tried in this blog over the years to provide insight to the reader that explains why cancer is an atrocious disease and at times how cancer patients and survivors feel. There is an excerpt in the book which resonated with me that may help one not touched directly by this disease understand how patients experience cancer. It was written in an essay titled A View from the Front Line, by Maggie Jencks.

Maggie was diagnosed with breast cancer in 1988. She was treated with a lumpectomy and then a mastectomy. For several years she considered herself cured, but five years later she relapsed with metastatic breast cancer to her organs and bones. Aggressive chemotherapy failed and she died in 1995. Her analogy to cancer begins with her being awoken up mid-flight on a jumbo jet and thrown out with a parachute into a foreign landscape without a map. Here’s her essay…

“There you are, the future patient, quietly progressing with other passengers toward a distant destination when, astonishingly (why me?) a large hole opens in the floor next to you. People in white coats appear, help you into your parachute and - no time to think - out you go.

You descend. You hit the ground… But where is the enemy? What is the enemy? What is it up to? … No road. No compass. No map. No training. Is there something you should know and don’t?

The white coats are far far away, strapping others into their parachutes. Occasionally they wave but, even if you ask them, they don’t know the answers. They are up there in the Jumbo, involved with parachutes, not map-making.”

Although written over 15 years ago, the image, for me, still captures the desolation and desperation of many cancer patients. Oncology researchers, obsessed with radical and aggressive therapies, were devising newer parachutes, but with no systemic maps of the quagmire to guide patients and doctors. This is less true today than in the mid 1990s, but more progress is beneficial.

I realize this is a long blog entry, but I would be remiss in not sharing with you some further highlights from the book. Here they are in no particular order.
  • The profession of oncology got its start based on the observation of the effects of mustard gas in WW I. This seems highly ironic.
  • Ether, the first anesthetic, was not in use until the late 1800s. Mastectomies have been documented back to 500 B.C. I think back to all those poor women.
  • If we don’t kill the tumor, we kill the patient. This short simple statement reflects why cancer doctors and researchers take such an aggressive treatment approach. You may have to read it a few times to get its full meaning.
  • The pap smear was named after George Papanicolaous, a Greek cytologist at Cornell University. He began human trials in the late 1920s. It wasn’t until 30 years later that his earlier discovery began to become a mainstream cancer prevention procedure. For most of his career, he was ridiculed and ignored by his peers as discovering a useless procedure. The ironies in the book abound.
  • The cancer genome project is in progress and is focused on mapping every cancer gene in every type of cancer. When complete it is estimated to be 10,000 times the size of the human genome project.
  • We are winning the war on cancer; it just so happens to be a very long and complicated march.
I’ll stop my highlights here, but there were dozens of others such as the effect politics, fund raising, the tobacco industry, dedicated researchers / physicians, care providers, patients, other diseases (e.g., polio and HIV) and cancer advocates have shaped where we are today in the war on cancer.

I'd like to take this opportunity to thank my friends, family, physicians, and researchers for their continued support and effort.  It feels good to be celebrating my Cancerversary today.

Take care everyone and Happy Holidays.

Thursday, December 2, 2010

Swallowing Difficulties

The technical term for swallowing difficulties is dysphagia. My diagnosis, based on the results of a fluoroscope test interpreted by a highly trained speech therapist is severe dysphagia. I've written about this in my blog many times as it is the bane of my existence. I am continuing my quest to not just live with this issue, but to somehow fix it. This is partly due to wanting a better life for myself (who doesn't) and partly due to a case of OCD. I have trouble adjusting to things that are broken. In my case, my throat is broken and my ability to truly adapt to it wavers from partial acceptance to "just not going to take it anymore."

I came across an article yesterday (12/1/10) that caught my attention. A Uruguayan physician who is also a oral cancer survivor designed a small very simple implant which has allowed him to drink orally (versus a feeding tube) for the first time in 2 years. The operation was performed in a 45 minute procedure by two UC Davis physicians. Here's a link to the article.

http://www.healthcanal.com/surgery-rehabilitation/12808-Davis-surgeons-test-innovative-device-patient-with-swallowing-disorder.html

What caught my attention was the simplicity of the solution. It is not a panacea for all swallowing issues, but it could help thousands of people quickly and at a low cost. This may allow the patient in this article to live without a feeding tube. The estimated cost (based on other articles I have read) of a feeding tube per patient is $31,000 annually in medical expenses.

For myself, there are four separate issues which have lead to my diagnosis of severe dysphagia.

1) A dime sized hole in my soft palate which prohibits the ability of my swallowing function to create a proper vacuum (or suction) during the swallowing process,

2) Removal of part of my epiglottis which, if it were all there, would protect my airway during swallowing,

3) Removal of tongue and throat nerves which, when intact, help control muscles that make swallowing possible, and

4) Scaring in my upper esophagus (a result of radiation, chemo, and surgery) which have fused parts of my anatomy together that would, under normal circumstances, be working synergisticly and independently.

Here's my plan. First, I'm looking at options for patching the hole in my soft palette (issue #1 above). The Mayo Clinic is doing some leading edge work with Transoral Robotic Surgery for Oral Cancer. I plan to contact them as well as my own cancer center to explore options in this area. Second, I'll be reaching out to the physicians noted in the above article to explore the appropriateness and possibility of a device and operation similar to the one described in the article. This could address above issues #3 and #4. Issue #2, patching my epiglottis, is very unique to my particular situation. For that, I'll consult with my network of health care providers.

Although I began focusing on this set of potentially corrective actions yesterday, I view the exploration of this taking place over a six month time frame. Hey, Rome wasn't built in a day and the same can be said for what it might take to address my swallowing disorder.

Take care everyone.

Ed

Sunday, October 31, 2010

The Cancer Sleeper Cell

I continue to read about cancer; my type of cancer and cancers in general. I have four primary sources: 1) The daily Wall Street Journal, 2) The Sunday New York Times, 3) friends/family who send me articles, and 4) Google alerts. For those not familiar with Google alerts, it is a Google feature which allows one to set up specific searches to run continuously, daily, or weekly for subjects in which one has an interest. This is where I find most of my cancer-related reading materials. For more information on Google Alerts, just google it.

Today's Sunday New York Times Magazine section had a fascinating research-oriented articles on cancer stem cells, "The Cancer Sleeper Cell." It's a long article, but provided added insight into my understanding of how important it would be to fighting relapses if one could identify, isolate, and destroy the cancer stem cell. What the article highlighted for me was that researchers believe that only one bad cell in a million bad cancer leukemia (a blood cancer) cells is a stem cell which can cause a relapse. The hypothesis being that if they can kill that one cell in a million, they can stop the cancer from relapsing. They were able to take this finding and apply it to various solid tumors. It also raised other important questions about what defines a cure and how to measure a treatment's success.

I was able to Google the article and the link is...

http://www.nytimes.com/2010/10/31/magazine/31Cancer-t.html

For those that are interested, enjoy this somewhat intellectually challenging reading. Take care everyone.

Ed