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Cancer

Cancer, Health Policy, NIH, Public Health

Draining the cancer swamp

Draining the cancer swamp

4011473415_46405053bd_zThere’s an old adage that applies to many difficult situations that we face in life: When you’re up to your armpits in alligators, it’s difficult to remind yourself that you should have drained the swamp.

I’ve come to view cancer as a vicious predator lurking in dark waters, eager to attack one out of two of us in our lifetimes. Cancer is the second most common cause of death in the United States.

Looking at the current national funding model for cancer research, I wonder if society has lost track of a vital goal: preventing cancer, not just treating it. Wouldn’t it be better if we prevented cancer in the first place? Cancer prevention would reduce the devastating physical, psychological, emotional, social and economic burden placed on patients, their families and their friends.

As he stepped down from the role of Director of the National Cancer Institute, Harold Varmus, MD, spoke about the deep complexity of cancer and the tremendous amount of basic research that needs to be done. While recognizing the need for clinical testing, he also called for more pioneering discoveries into who gets cancer, where and why.

The financial constraints facing scientific research force us to make difficult choices. Right now, our current health-care model prioritizes “identifiable individuals” over “statistical individuals.” Identifiable individuals are those real persons in distress who have been diagnosed with cancer. They need treatment, and we are highly motivated to help cure them. The cost of doing so, however, is high: The average monthly cost of cancer treatment has more than doubled to $10,000 over the last decade. Of course, we are willing to pay the costs – these victims are our mothers, our fathers, our sons and our daughters.

Statistical individuals are those who may be at risk, but they may not know it. They may never know that scientific research “rescued” them from a devastating disease. Through prevention measures enacted by individuals themselves (e.g., getting more exercise, avoiding tobacco use) or by society (e.g., limiting chemical exposures in the environment, banning the use of tanning beds for minors), these individuals may be able to escape the scourge of cancer.

When making choices about where to invest limited dollars, it is so much easier to say “no” to statistical people rather than real people.

I don’t advocate taking money away from cancer treatment, but I do advocate a greater investment of federal dollars in research that leads to reducing the incidence of cancer in the healthy population. By tracking and analyzing patterns and trends of cancer, we can identify potential risk factors and inform individuals and communities about positive changes they can make toward living cancer-free lives.

It is estimated that over 50 percent of the 585,720 cancer deaths in the U.S. in 2014 were related to preventable causes. As such, federal dollars directed toward statistical individuals will save both money and lives.

We need to drain the swamp. Our ultimate societal goal shouldn’t be to treat cancer more effectively, but to prevent it altogether. We need to intervene as early as possible in the trajectory of cancer. By doing so, we will greatly reduce the extent and depth of human suffering.

Donna Randall, PhD, is chief executive officer of the Cancer Prevention Institute of California.

Photo by William Warby

Big data, Cancer, Genetics, Immunology, Research, Science, Stanford News

Linking cancer gene expression with survival rates, Stanford researchers bring “big data” into the clinic

Linking cancer gene expression with survival rates, Stanford researchers bring "big data" into the clinic

Magic 8 ball“What’s my prognosis?” is a question that’s likely on the mind, and lips, of nearly every person newly diagnosed with any form of cancer. But, with a few exceptions, there’s still not a good way for clinicians to answer. Every tumor is highly individual, and it’s difficult to identify anything more than general trends with regard to the type and stage of the tumor.

Now, hematologist and oncologist Ash Alizadeh, MD, PhD; radiologist Sylvia Plevritis, PhD; postdoctoral scholar Aaron Newman, PhD; and senior research scientist Andrew Gentles, PhD, have created a database that links the gene-expression patterns of individual cancers of 39 types with the survival data of the more than 18,000 patients from whom they were isolated. The researchers hope that the resource, which they’ve termed PRECOG, for “prediction of cancer outcomes from genomic profiles” will provide a better understanding of why some cancer patients do well, and some do poorly. Their research was published today in Nature Medicine.

As I describe in our release:

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. By doing so, it may be possible to learn what has gone wrong in the cancer cells, and give ideas as to how best to block the cells’ destructive growth. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

Instead, the researchers pulled back and sought patterns that might become clear only when many types of cancers, and thousands of patients were lumped together for study:

Gentles and Alizadeh first collected publicly available data on gene expression patterns of many types of cancers. They then painstakingly matched the gene expression profiles with clinical information about the patients, including their age, disease status and how long they survived after diagnosis. Together with Newman, they combined the studies into a final database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” said Alizadeh. “Then we could ask what we could learn more broadly.”

The researchers found that they were able to identify key molecular pathways that could stratify survival across many cancer types:

In particular, [they] found that high expression of a gene called FOXM1, which is involved in cell growth, was associated with a poor prognosis across multiple cancers, while the expression of the KLRB1 gene, which modulates the body’s immune response to cancer, seemed to confer a protective effect.

Alizadeh and Plevritis are both members of the Stanford Cancer Institute.

Previously: What is big data?Identifying relapse in lymphoma patients with circulating tumor DNA,  Smoking gun or hit-and-run? How oncogenes make good cells go bad and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Photo by CRASH:candy

Applied Biotechnology, Big data, Cancer, Genetics, Research, Science, Stanford News

Peeking into the genome of a deadly cancer pinpoints possible new treatment

Peeking into the genome of a deadly cancer pinpoints possible new treatment

small cell lung cancerSmall cell lung cancer is one of the most deadly kinds of cancers. Typically this aggressive disease is diagnosed fairly late in its course, and the survival rates are so dismal that doctors are reluctant to even subject the patient to surgery to remove the tumor for study. As a result, little is known about the molecular causes of this type of cancer, and no new treatments have been approved by the Food and Drug Administration since 1995.

Now a massive collaboration among researchers around the world, including the University of Cologne in Germany and Stanford, has resulted in the collection of more than 100 human small cell lung cancer tumors. Researchers sequenced the genomes of the tumors and identified some key steps in their development. They also found a potential new weak link for treatment.

The findings were published today in Nature, and Stanford cancer researcher Julien Sage, PhD, one of three co-senior authors of the paper, provided some details in an email:

With this larger number of specimens analyzed, a more detailed picture of the mutations that contribute to the development of small cell lung cancer now emerges. These studies confirmed what was suspected before, that loss of function of the two tumor suppressor genes, Rb and p53, is required for tumor initiation. Importantly, these analyses also identified new therapeutic targets.

The researchers also saw that, in about 25 percent of cases, the Notch protein receptor was also mutated. This protein sits on the surface of a cell; when Notch binds, it initiates a cascade of signaling events within the cell to control its development and growth. As Sage explained:

The mutations in the Notch recepetor were indicative of loss of function, suggesting that Notch normally suppresses small cell lung cancer development. Indeed, when graduate student Jing Lim in my lab activated Notch in mice genetically engineered to develop small cell lung cancer, we found a potent suppression of tumor development. These data identify the Notch signaling pathway as a novel therapeutic target in a cancer type for which new therapies are critically needed.

This is not Sage’s first foray into fighting small cell lung cancer. In 2013, he collaborated with other researchers at Stanford, including oncologist Joel Neal, MD, PhD, to identify a class of antidepressants as a possible therapy for the disease.

Previously: Gene-sequencing rare tumors – and what it means for cancer research and treatment, Listening in on the Ras pathway identifies new target for cancer therapy and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Image by Yale Rosen

Cancer, Clinical Trials, Dermatology, Genetics, Pain, Pediatrics, Research, Stanford News

The worst disease you’ve never heard of: Stanford researchers and patients battle EB

The worst disease you've never heard of: Stanford researchers and patients battle EB

EB patient and docsI’m often humbled by my job. Well, not the job, exactly, but the physicians, researchers, and especially patients who take the time to speak with me about their goals and passions, their triumphs and fears. Their insight helps me as I struggle to interpret what goes on here at the Stanford University School of Medicine for others across the university and even around the world.

But every once in a while, an article comes along that brings me to my (emotional) knees. My article “The Butterfly Effect” in the latest issue of Stanford Medicine magazine describes the toll of a devastating skin disease called epidermoloysis bullosa on two young men and their families, as well as the determined efforts of a dedicated team of doctors and scientists to find a treatment. As a result, Stanford recently launched the world’s first stem-cell based trial aimed at correcting the faulty gene in the skin cells of patients with a severe form of the condition, which is often called EB.

I trace the path of one family as they learn, mere hours after his birth, that their son, Garrett Spaulding, has EB, which compromises the ability of the outer layers of the to stick together during friction or pressure. Patients develop large blisters and open wounds over much of their bodies. It’s incurable, fatal, and nearly indescribably painful. Paul Khavari, MD, PhD, now the chair of Stanford’s Department of Dermatology, was a young doctor at the time newborn Garrett was admitted to Lucile Packard Children’s Hospital Stanford in 1997.

“His whole body, his skin was blistered and falling off everywhere someone had touched him,” Khavari recalls in the article. “His parents were devastated, of course, at a time that was supposed to be one of the most joyful of their lives.”

Garrett’s now 18 years old, but the disease is taking its toll.

You’ll also meet Paul Martinez, one of the first participants in Stanford’s new clinical trial. He’s 32, which makes him an old man in the EB community. Unlike many EB patients, he has finished high school and completed a college degree in business marketing with a dogged determination that makes me ashamed of my petty complaints about my minor life trials. And he’s done it without relying on the pain medications essential for most EB patients. As he explains in the article:

We don’t know what it is like to not be in pain. It’s just normal for us. […] I have a very high tolerance, and don’t take any pain medication. I cherish my mind a lot. Rather than feel like a zombie, I prefer to feel the pain and feel alive.

Continue Reading »

Aging, Cancer, Dermatology, Genetics, Research, Stanford News

Genetic secrets of youthful skin

Genetic secrets of youthful skin

new hatEvery year, upwards of $140 billion a year gets spent on cosmetics. In the United States alone, says an authoritative report, a recent year saw upwards of 5.6 million Botox procedures, 1.1 million chemical peels, almost a half-million laser skin procedures, 196,286 eyelid surgeries and a whole bunch of face lifts.

If you’ve got the courage to compare your present-tense face with the one you were wearing 20 or even 10 years ago, you’ll see why. As I wrote in a just-published Stanford Medicine article, “Wither youth?”:

The terrain of aging skin grows all too familiar with the passing years: bags under the eyes, crow’s feet, jowls, tiny tangles of blood vessels, ever more pronounced pores and pits and pigmentation irregularities. Then there are wrinkles — long, deep “frown lines” radiating upward from the inside edges of the eyebrows and “laugh lines” that trace a furrow from our nostrils to the edges of our lips in our 40s, and finer lines that start crisscrossing our faces in our 50s. Sagging skin gets more prominent in our later years as we lose bone and fat.

“And,” I added wistfully, “it’s all right there on the very outside of us, where everyone else can see it.”

Stanford dermatologist Anne Chang, MD, who sees a whole lot of skin, got to wondering: Why does skin grow old? Armed with a sophisticated understanding of genetics, she went beyond lamenting lost youth and resolved to address the question scientifically, asking: “Can you turn back time? Can aging effects be reversed? Can you rejuvenate skin, make it young again?”

The answers she’s come up with so far – from hereditary factors to a possible underlying genetic basis for how some treatments now in common commercial cosmetic use (such as broadband light therapy) could potentially slow or even reverse the aging of skin – are described in my magazine article.

Previously: This summer’s Stanford Medicine magazine shows some skinResearchers identify genetic basis for rosacea, New study: Genes may affect skin youthfulness and Aging research comes of age
Photo by thepeachpeddler

Bioengineering, Cancer, Imaging, Microbiology, Research, Science, Stanford News

Stanford team develops technique to magnetically levitate single cells

Stanford team develops technique to magnetically levitate single cells

Remember the levitating frog? That feat — the levitation of a live frog using a powerful magnet — was awarded the 2000 Ig Nobel Prize. Fascinating to watch, the demonstration also cemented a longstanding belief that levitating anything smaller than 20 microns was flat-out impossible. Much less something alive.

Not so, a team of Stanford-based researchers showed in a paper published today in the Proceedings of the National Academy of Sciences (PNAS). Using a 2-inch-long device made of two magnets affixed with plastic, the team showed it’s possible to levitate individual cells.

The video above demonstrates the technique in a population of breast cancer cells. Originally, the cells hover, suspended between the two magnets. But when exposed to an acid, they start to die and fall as their density increases.

“It has very broad implications in multiple diseases including cancer, especially for point-of-care applications where it can bring the central lab diagnostics to the comfort of patients’ homes or physicians’ office,” Utkan Demirci, PhD, a co-senior author and associate professor of radiology, told me.

The technique makes it possible to distinguish healthy cells from cancerous cells, monitor the real-time response of bacteria or yeast to drugs and distinguish other differences between cells that were thought to be homogenous, said Naside Gozde Durmus, PhD, a postdoctoral research fellow and first author of the paper.

Critically, the technique does not require treating the cells with antibodies or other markers, Durmus said. That ensures the cells are not altered by any treatments and makes the technique easy to use in a variety of settings, including potentially in physicians’ offices or in resource-poor settings.

The device works by balancing the gravitational mass of a cell against its inherent magnetic signature, which is negligible when compared with the cell’s density, Durmus said.

Interestingly, however, the cells — or bacteria treated with an antibiotic — do not die at the same rate, providing hints at their individual adaptations to environmental stressors, said co-senior author Lars Steinmetz, PhD, a professor of genetics.

To enhance the precision of the technique, the researchers can tweak the concentration of the solution that holds the cells, Durmus said. A highly concentrated solution allows for the differentiation of cells of similar densities, while a less concentrated solution can be used to examine a population of heterogeneous cells.

The team plans to investigate the applications of the device next, including its use in resource-poor settings where the cells can be observed using only a lens attached to an iPhone, Durmus said.

Previously: Harnessing magnetic levitation to analyze what we eat, Researchers develop device to sort blood cells with magnetic nanoparticles and Stanford-developed smart phone blood-testing device wins international award
Video courtesy of Naside Gozde Durmus

Cancer, Patient Care, Research, Stanford News

From petri dish to patient: Studying, treating – and trying to cure – less common cancers

From petri dish to patient: Studying, treating - and trying to cure - less common cancers

surviving melonomaIn 2015, more than 1.5 million Americans were diagnosed with cancer. Around forty percent of those new diagnoses were in three types of cancer — breast, lung, and prostate —  so it’s no surprise that those are the ones you hear about most often. But hundreds of thousands of new cancer patients each year are diagnosed with less common cancers, some affecting only a handful of patients a year. These are the diseases you don’t often hear about.

Before a few months ago, I have to admit that I didn’t know anything about cutaneous T cell lymphoma (CTCL). Each year, just a few thousand adults in the U.S. are diagnosed with the cancer, which often starts as an itchy, scaly rash — not the first thing that comes to mind when you think of classic cancer symptoms. Most people first learn about CTCL when they, or someone close to them, is diagnosed. I, on the other hand, started investigating it because I was writing about Stanford’s Cutaneous Lymphoma Group, which is spearheading research and new treatments of the disease.

At the same time, I was researching metastatic melanoma, the most advanced form of the skin cancer. While melanoma of any variety is relatively common (almost 75,000 new cases a year in the U.S.), only four percent of new diagnoses are the most severe, metastatic type. To understand both CTCL and metastatic melanoma, I spoke to patients being treated at Stanford clinics, doctors who specialize in the diseases, and researchers who study the cancers at the most basic molecular and genetic levels.

Science writers and scientists alike often justify research on rare diseases by explaining how we can learn about more common conditions through studying less common ones. But hearing about melanoma and CTCL — and how findings in the lab quickly trickle up to change clinical practice and save patients’ lives — it became ever clearer to me that research on these rarer cancers has an immeasurable impact all on its own. The clinicians I talked to were all avid proponents of integrating the latest research into their practices as soon as they could, and constantly tweaking their protocols to find the best ways to help patients. And each patient was able to get a new lease on life thanks to clinical trials and scientist-doctors willing to try new things.

To learn more about CTCL and metastatic melanoma, check out my features in the latest issue of Stanford Medicine magazine: “The rarest of rashes,” and “Surviving melanoma.”

Sarah C.P. Williams is an award-winning science writer covering biology, chemistry, translational research, medicine, ecology, technology and anything else that catches her eye.

Previously: This summer’s Stanford Medicine magazine shows some skinGene-sequencing rare tumors – and what it means for cancer research and treatmentA rare cancer survivor’s journey to thriving and advocatingHumble anti-fungal pill appears to have a noble side-effect: treating skin cancer and Raising awareness about rare diseases
Illustration by Matthew Bandsuch

Cancer, Dermatology, Infectious Disease, Stanford News, Transplants

This summer’s Stanford Medicine magazine shows some skin

This summer's Stanford Medicine magazine shows some skin

below surface banner and 1 blogSkin is superficial, literally. But it’s also really deep, as I realized while editing the just-published issue of Stanford Medicine magazine. The summer issue features the special report “Skin deep: The science of the body’s surface.”

I learned from the chair of Stanford’s Department of Dermatology, Paul Khavari, MD, PhD, that thousands of diseases affect the skin. And I learned it’s surprisingly abundant: An average-sized adult is covered with about 20 square feet of skin.

Research on skin is thriving, in part, because skin is so easy to get hold of, Khavari told me. “The accessibility of skin tissue to the application of new technologies, including genomics, proteomics, and metabolomics, make this a watershed moment for progress in alleviating the tremendous suffering caused by the global burden of skin disease,” he said.

The magazine, produced with support from the dermatology department, includes articles not only about new treatments, but also insights into how skin works when it’s healthy and how to keep it that way. In a Q&A and audio interview, actress and playwright Anna Deavere Smith, who is African-American, addresses skin’s social meaning, discussing her relationship to her own skin and how, as a writer and actor, she gets under the skin of her characters. The online version of the magazine includes audio of an interview with Smith.

Also in the issue:

  • The butterfly effect“: A story about two young men coping with one of the world’s most painful diseases — the skin-blistering condition epidermolysis bullosa — including news about an experimental treatment to replace their broken genes. The online version includes a video with a patient at home and interviews with experts on the condition.
  • Surviving melanoma“: A report on progress being made after years of stagnation in treating the most deadly skin cancer: melanoma.
  • The rarest of rashes“:  A look at one of Stanford Medicine’s great accomplishments in dermatology: successful treatment of a rare but dangerous rash — cutaneous lymphoma, a form of blood cancer that spreads to the skin.
  • Take cover“: Tips on keeping skin safe from the sun.
  • Wither youth“: A feature on research seeking to answer the question: Why does skin age?
  • New lungs, new life“: The story of a young woman who lost her smile and had it restored through surgery.

The issue also includes a story considering the rise in number of castoff donor hearts, despite a shortage of the organs for transplants, and an excerpt from Jonas Salk: A Life, a new biography of the polio-vaccine pioneer, written by retired Stanford professor Charlotte Jacobs, MD.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Stanford Medicine magazine traverses the immune system and Stanford Medicine magazine opens up the world of surgery
Photo, from the Summer 2015 issue of Stanford Medicine, by Max Aguilera-Hellweg

Cancer, Medical Education, Medicine and Society, Patient Care

Cancer Ninja fights patient misinformation, one cartoon at a time

Screen Shot 2015-06-15 at 1.16.14 PMThere seems to be a trend towards using cartoons for health education: In just the past few months, we’ve posted on children’s books, depression blogs, global-health videos, and art-based clinical skills, all using non-realist art to convey information and qualitative experience. A new blog by Andrew Howard, MD, radiation oncologist at the University of Chicago and the University of Illinois at Chicago, fits right in with this innovative bunch. His blog, Cancer Ninja, aims to use cartoons to convey both how cancer works and what it’s like to be diagnosed and treated for it. Howard started it just one month ago, so his project was fresh from the creative oven when I spoke with him on the phone last week.

What motivated you to start Cancer Ninja?

I’d been frustrated for a while with how little my patients know about cancer. They come in with all these confusions; they don’t understand the difference between chemotherapy and radiation (and from a doctor’s perspective, there’s a huge difference). They don’t understand our rationale for choosing one treatment or another or a combination. One patient was convinced that hot sauce caused cancer and was really upset that she had gotten cancer because she had gone out of her way to avoid hot sauce all of her life. I realized there is a lot of misinformation out there, and that was the purpose for starting this blog.

My wife and I have two little girls, and in the evenings sometimes they say, ‘Draw dinosaurs with me, Daddy!’ So I started drawing with them, and I enjoyed it so much that I would sometimes stay up at night after they had gone to bed, still working on my dinosaur. My wife saw me enjoying that a lot, and thought maybe I could combine this with educating people about cancer.

Your website is targeted to be generally informative about cancer; why did you start with breast cancer? 

Breast cancer is really common in this country, unfortunately, and it’s also very well studied, so we understand a lot about it, which makes it a nice model. There’s a pretty clear algorithm for the proper way to treat a patient with such and such stage breast cancer, so it makes it easy to follow along.

How many characters or episodes are you hoping to do? So far, there’s just “Jane.” 

Screen Shot 2015-06-16 at 1.36.59 PMI’m kind of experimenting. I envision that I’m going to follow Jane though her diagnosis and treatment, but my wife told me that Jane can’t die; she really likes Jane. But 40 percent of people with cancer will ultimately die of their disease, so I want to draw and write about what it’s like to be confronting one’s death, at least as I have witnessed it. What can medicine offer those people, and what can’t it? So I want to introduce a character who dies. I feel like there’s so much that’s already happened in Jane’s story, and I could go back and fill in the details. The mutation steps that turn a cell into a cancer cell, that’s actually a really complicated transformation that I could explore in greater depth.

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Cancer, Imaging, Research, Stanford News, Surgery

Better tumor-imaging contrast agent: the surgical equivalent of “cut along dotted line”?

cut horseIt would be tough for most people to take a snubbed-nose scissors to an 8-1/2″ x 11″ sheet of blank paper and carve out a perfect silhouette of, say, a horse from scratch. But any kid can be an artist if it means merely cutting along a boundary separating two zones of different colors.

Tumor-excision surgery requires an artist’s touch. It can be tough to distinguish cancerous from healthy tissues, yet the surgeon needs to approach perfection in precisely removing every possible trace of the tumor while leaving as much healthy tissue intact as possible. To help surgeons out, technologists have been designing contrast agents that target only tumor cells, thus providing at least a dotted line for scalpel wielders.

Stanford pathologist and molecular-probe designer Matthew Bogyo, PhD, in a study published in ACS Chemical Biology, has now demonstrated, using mouse models of breast, lung and colon cancer, the effectiveness of a fluorescence-emitting optical contrast agent that selectively accumulates in tumors and can be used to guide surgery. In effect, the probe lights up the tumor, providing a convenient, high-resolution dotted line for its excision.

Perhaps more striking, the new study showed that this probe, designed by Bogyo’s group, is compatible with a robotic remote minimally invasive surgery system that is already enjoying widespread commercial use. Intuitive Surgical, Inc., the company that sells this system, collaborated on the study.

Previously: Stanford researchers explore new ways of identifying colon cancer, Cat guts, car crashes, and warp-speed Toxoplasma infections and Compound clogs Plasmodium’s in-house garbage disposal, hitting malaria parasite where it hurts
Photo by Merryl Zorza

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