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Cancer, Clinical Trials, In the News, NIH, Patient Care, Research

National Cancer Institute looking for “Exceptional Responders”

OLYMPUS DIGITAL CAMERAHope is a powerful force in cancer treatment. For patients and their families, the hope is that, no matter how unlikely, the treatment plan will cure the patient and eradicate the disease. Sadly, this is sometimes a long shot. But sometimes, against all odds, the therapy is unusually successful. Now the National Cancer Institute is trying to learn why.

This week the institute launched a study into the phenomena of “Exceptional Responders” – that is, cancer patients who have a unique response to treatments (primarily chemotherapy) that have not been effective for most other patients. As they describe in a Q&A about the effort:

For this initiative, exceptional responders will be identified among patients enrolled in early-phase clinical trials in which fewer than 10 percent of the patients responded to the treatments being studied; patients who were treated with drugs not found to be generally effective for their disease; patients who were treated in later-phase clinical trials of single agents or combinations; and even patients who were treated with established therapies. In this pilot study, malignant tissue (and normal tissue, when possible) and clinical data will be obtained from a group of exceptional responders and analyzed in detail. The goal is to determine whether certain molecular features of the malignant tissue can predict responses to the same or similar drugs.

The researchers would like to obtain tumor samples, as well as normal tissue, from about 100 exceptional responders. They’ll compare DNA sequences and RNA transcript levels and other molecular measurements to try to understand why these patients were such outliers in their response to treatment. In at least one previous case, an exceptional responder with bladder cancer led researchers to discover a new molecular pathway involved in the development of the disease, and suggested new therapeutic approaches for other similar patients.

Do you know someone who might qualify for the study? More from the Q&A:

Patients who believe they may be exceptional responders should contact their physicians or clinical trialists to see if they can assist in submitting tissue for consideration. [...] Investigators who have tissue from a potential exceptional responder should send an email to NCIExceptionalResponders@mail.nih.gov. The email should include a short description of the case, without patient identifiers; information about whether tissue collected before the exceptional response is available; whether informed consent was given to use tissue for research; and the patient’s vital status.

Photo by pol sifter

Cancer, Global Health, Health Policy, Infectious Disease, Public Health

Treating an infection to prevent a cancer: H. pylori and stomach cancer

Treating an infection to prevent a cancer: H. pylori and stomach cancer

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The number of newly diagnosed stomach cancer cases in the United States is less than a tenth of the number of prostate cancer cases or breast cancer cases, which may be part of the reason it doesn’t get the same attention as breast and prostate cancer. But the mortality rate is much higher for stomach (or gastric) cancer. Nearly 11,000 Americans will likely die from gastric cancer this year, with only 28 percent of cases surviving five years or more. For comparison, the five-year survival rate for prostate cancer is nearly 99 percent and for breast cancer, it’s more than 89 percent.

On a global scale, an estimated 700,000 people will die from gastric cancer this year, as Stanford infectious disease specialist Julie Parsonnet, MD, and her co-authors note in a Viewpoint piece in the most recent issue of the Journal of the American Medical Association. The authors also point out that worldwide, about 77 percent of gastric cancer cases are linked to chronic infections of Helicobacter pylori, a helix-shaped bacteria that was identified in the early 1980s and found to be linked to gastric ulcers a few years later, as well as to gastritis, an inflammation of the stomach lining that is a precursor to stomach cancer.

Researchers are still trying to understand exactly how H. pylori causes cancer or even how it colonizes the gastrointestinal track – they believe it’s picked up via food or water. Until recently, there was a dearth of randomized clinical trials that looked at the effectiveness of screening and treatment for H. pylori as a method for preventing stomach cancer.

Ignoring gastric cancer in the hope that it will soon disappear is not a tenable health policy

In the opinion piece, the authors describe the recommendations of a working group that met in December 2013 at the behest of the International Agency for Research on Cancer. Taking the burden of the disease and the availability of treatment options in consideration, the group considered gastric cancer “a logical target for intervention,” according to the authors of the JAMA piece. They go on to write:

Screening and treatment for H pylori is generally acceptable and affordable. An inexpensive serological test can determine who may be infected, with a sensitivity and specificity that could be sufficient for population-based prevention programs. Low-cost treatment regimens using 2 or 3 generic antibiotics plus a proton pump inhibitor for 7 to 14 days can eradicate the infection in more than 80% of cases, depending on the antibiotic resistance patterns of H pylori within the population. Economic modeling studies indicate that H pylori screening and treatment strategies are cost-effective under a large range of assumptions about effectiveness and costs. However, the models are limited by reliance on observational data rather than randomized trial results, by a lack of information on possible adverse effects of treatment, and by limited data from lower-income countries.

Researchers still have many gaps in their understanding of the best methods to prevent stomach cancer, but several trials may answer some of those questions in the coming decade.

Stomach cancer is not the only cancer known to be linked with an infection. Doctors routinely test whether women who come in for a PAP smear are infected with the human papilloma virus (HPV), which is linked to cervical cancer. Chronic hepatitis B and C infections are known to be linked to liver cancer. In time, screening for H. pylori to prevent stomach cancer may become routine. Until then, Parsonnet and her coauthors say in their conclusion, “Ignoring gastric cancer in the hope that it will soon disappear is not a tenable health policy.”

Previously: Researchers identify potential drug target in ulcer bug that infects half the world’s population, Good-bye cancer, good-bye stomach: A survivor shares her tale and Image of the Week: Helicobacter pylori colonizing the stomach
Photo by Shuman Tan and Lydia-Marie Joubert

Applied Biotechnology, Bioengineering, Cancer, Research, Stanford News

New “decoy” protein blocks cancer from spreading

New "decoy" protein blocks cancer from spreading

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Cancer becomes most deadly when it’s on the move – jumping from the breast to the brain or the pancreas to the liver and then onward.

But now, a team of Stanford researchers led by radiation biologist Amato Giaccia, PhD, and bioengineer Jennifer Cochran, PhD, have created a protein that may be able to thwart the metastasis.

They published their results this week in Nature Chemical Biology.

“This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” Giaccia said in a Stanford release. ”It could open up a new approach to cancer treatment.”

The researchers created a protein that mimics Axl, a protein found on the surface of cancer cells. This decoy protein intercepts incoming messages – intended for the original Axl – cueing the cancer cells to find a new home.

The decoy Axl worked wonders in mice. Mice with breast cancer given the treatment had 78 percent fewer new tumors, and mice with ovarian cancer had 90 percent fewer new tumors than mice with cancer not given the treatment.

Becky Bach is a former park ranger who now spends her time writing about science or practicing yoga. She’s a science-writing intern in the Office of Communications and Public Affairs.

Previously: Studying the drivers of metastasis to combat cancer, A computer kit could lead to a better way to design synthetic molecules, Common drug class targets breast cancer stem cells, may benefit more patients, says study
Photo by Rod Searcey

Cancer, Health and Fitness, Research

Exercise may boost effectiveness of chemotherapy

Exercise may boost effectiveness of chemotherapy

running_092214Staying physically active during chemotherapy treatment can benefit patients’ physical and mental health. But findings from an animal study show that exercising may also help reduce the size of tumors.

As reported by Futurity, University of Pennsylvania researcher Joseph Libonati, PhD, and colleagues originally set out to test whether adding a fitness regimen to chemotherapy would offset cardiac damage related to the drug doxorubicin. While the team failed to find any significant evidence that exercise provided protection against negative cardiac side-effects, they did find that mice that exercised while receiving chemotherapy had notably smaller tumors than those that had chemotherapy alone. From the article:

Further studies will investigate exactly how exercise enhances the effect of doxorubicin, but the researchers believe it could be in part because exercise increases blood flow to the tumor, bringing with it more of the drug in the bloodstream.

“If exercise helps in this way, you could potentially use a smaller dose of the drug and get fewer side effects,” Libonati says. Gaining a clearer understanding of the many ways that exercise affects various systems of the body could also pave the way for developing drugs that mimic the effects of exercise.

“People don’t take a drug and then sit down all day,” he says. “Something as simple as moving affects how drugs are metabolized. We’re only just beginning to understand the complexities.”

Previously: Stanford preventive-medicine expert: Lay off the meat, get out the sneaks, From leukemia survivor to top junior golfer, Examining exercise and cancer survivorship and Study shows benefits of exercise for patients with chronic health conditions
Photo by MilitaryHealth

Cancer, Stanford News

Stanford Cancer Institute offers latest in cancer news, 140 characters at a time

Stanford Cancer Institute offers latest in cancer news, 140 characters at a time

Untitled-3 copyThe American Cancer Society’s 2014 annual report states that more than 1.6 million people in the U.S. will be diagnosed with cancer in the coming year. In response to this reality, many people try to arm themselves with as much information as possible about how to prevent, detect and/or treat the disease.

The Stanford Cancer Institute is committed to making cancer news and information more accessible and recently launched a new Twitter feed – @StanfordCancer – that delivers the latest developments in cancer research and clinical care from Stanford and around the world.

Combined with the Campaign for Stanford Medicine’s Transforming Cancer Care initiative, the Stanford Cancer Institute’s foray into social media is just one of Stanford Medicine’s many efforts to raise awareness about all the innovation scientists and physicians are pouring into disease detection, prevention and treatment.

Kylie Gordon works on the digital media team at Stanford University Communications. She received her undergraduate degree from Stanford in Modern Thought and Literature and has a graduate degree in Creative Writing from Northwestern University.

Biomed Bites, Cancer, Research

Discover the rhythms of life with a Stanford biologist

Discover the rhythms of life with a Stanford biologist

This is the second installment of our Biomed Bites series, a weekly feature that highlights some of Stanford’s most compelling research and introduces readers to innovative scientists from a variety of disciplines. 

What do giant bamboo plants — which flower once every 64 years — and cancer cells have in common? Both are governed by a biological cycle that Stanford professor James Ferrell, MD, PhD, is working to decipher. “We’re trying to figure out how these clocks work,” Ferrell says in the video above.

Ferrell says he has to use many tools familiar to physicists who work commonly with oscillations, although he studies living organisms as part of the burgeoning field of chronobiology.

Humans are governed by a network of closely rhythms, Ferrell explains:

We are intrinsically rhythmic organisms. We are a different person in the morning from the person we are in the evening. This might have profound consequences in terms of the proper way to treat disease.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Becky Bach is a former park ranger who now spends her time writing or on her yoga mat. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Studying the drivers of metastasis to combat cancer, Why sleeping in on the weekends may not be beneficial to your health, The key to speed? Inside the cell, it’s trigger waves 
Photo in featured entry box by Breezy Baldwin

Cancer, In the News, NIH, Research, Stanford News, Women's Health

NIH Director highlights Stanford research on breast cancer surgery choices

NIH Director highlights Stanford research on breast cancer surgery choices

The director of the NIH, Francis Collins, MD, this morning weighed in on a topic that has garnered much attention lately: the type of surgery that women diagnosed with breast cancer choose. The post, found at the NIH Director’s blog, describes a recent study by Stanford researchers published earlier this month in the Journal of the American Medical Association that examined survival rates after three different types of breast cancer surgery for women diagnosed with cancer in one breast: a lumpectomy (removal of the just the affected tissue, usually followed by radiation therapy), a single mastectomy (removal of the whole affected breast), and double mastectomy (removal of the unaffected breast along with the affected one.)

In a previous post we wrote in detail about the study and the finding that the number of double mastectomies in California have increased dramatically. However, except for women with the BRCA1 or BRCA2 genes, the procedure does not appear to improve survival rates for women who undergo the surgery compared with women who choose other types of breast surgery. Collins notes:

It isn’t clear exactly what prompted this upsurge in double mastectomy, which is more expensive, risky, and prone to complications than other two surgical approaches. But [researchers] Kurian and Gomez suggest that when faced with a potentially life-threatening diagnosis of cancer in one breast—and fears about possibly developing cancer in the other—women may assume that the most aggressive surgery is the best. The researchers also said it’s also possible that new plastic surgery techniques that achieve breast symmetry through bilateral reconstruction may make double mastectomy more appealing to some women.

Despite its recent upsurge in popularity, the study found double mastectomy conferred no survival advantage over the less aggressive approach of lumpectomy followed by radiation.

Collins also points out that the slightly worse survival rates of women who undergo single mastectomies probably reflect the fact that poorer women were more likely to have this surgery and is evidence of yet another health disparity linked to economic status.

Previously: Breast cancer patients are getting more bilateral mastectomies – but not any survival benefit

Cancer, Men's Health

So my life will be shorter than I’d hoped – what should I do differently?

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from Dave Staudenmaier.

“The news of your demise has been greatly exaggerated,” joked the surgeon when realizing I might have a rare slow-growing cancer instead of the horrifically aggressive and deadly adenocarcinoma of the pancreas that everyone thought I had.

He was right. I had “stage 4” Pancreatic Neuroendocrine Tumor metastasized to my liver. This was good news because it’s a slow-growing cancer.

Figuring out what to do with my life – not getting surgery – is what’s most urgent and important to me

It’s also the cancer that Steve Jobs had (and died from).

I fired my surgeon and my oncologist. Not because of his humor, but because of the urgency he placed on taking out my duodenum, gallbladder, spleen, part of my stomach and my entire pancreas in a “procedure” called a Whipple. No other options were considered or offered. No calls to a PNET specialist were made – so I found one on my own.

I was also told: There is no cure. There is no remission. Treatment options are limited and inconsistent. It’s possible that surgery might have bought me more time – but my new care team understood that I favored quality of life (hence my decision to opt out of surgery) over length of my life. And thankfully, some new treatments not available in Steve Jobs’ time have worked to shrink my tumors by sixty percent.

Though we’re fighting to keep the tumors from growing again for as long as possible, it sure looks like I won’t be around as long as I’d hoped. And though the drugs are helping control this beast, I know they won’t help forever and there will be pain and fatigue and other quality-of-life issues. So figuring out what to do with my life – not getting surgery – is what’s most urgent and important to me.

My work.  Should I quit my job like so many of my fellow PNET patients have? No way! I love my job, and it has only gotten better since my diagnosis. Seemingly by providence, last year my position was changed and I now head development of patient engagement software for the large health-care solutions firm I work for. I have the opportunity to directly help tens of millions of patients – patients like me.

My family. I have a wife and three teenagers. How can I create more time to make  memories with them while I still feel good? I now pay someone else to mow my lawn and perform those other maintenance services that previously consumed much of my weekend time. We live in Florida where there’s a lot of fun things to do as a family, so we do it – spending more time together than we used to. We also blew some savings for a family vacation to Turks and Caicos. We’ve never vacationed like that before and it was awesome – something that created good memories. I want to do something like that again.

My everyday life. Fewer things to worry about means less stress. After I was diagnosed, we gave away more stuff than we kept and we don’t miss it. All bills are now auto-paid so we don’t think about them and can’t miss a payment. We have one debit card and one credit card, and we pay for most things in cash.  And we learned to say “no,” as we limited our obligations to maximize our free time. I’ve also tried new things:  So far I’ve learned how to ride a horse and how to cook. Up next, skeet shooting.

I continue to rethink and reprioritize my life, and I’m thankful that my new care team understands what’s important to me and provides treatment that aligns with my goals.

Dave Staudenmaier is Senior Director of Development for Greenway Health, where he leads an awesome team creating software products benefiting patients and physicians. Dave continues to fight PNET with the support of his wife of 23 years and three children.

Previously: Managing a prostate cancer diagnosis: From leader to follower, and back again and A rare cancer survivor’s journey to thriving and advocating

Cancer, Dermatology, Research, Science, Stanford News

Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers

Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers

sunbathingA link between the UV rays in sunshine and the development of skin cancer is nothing new. We’ve all (hopefully) known about the damage sun exposure can wreak on the DNA of unprotected cells. But it’s not been known exactly how it causes cancers like squamous cell carcinoma or melanoma. Now, Stanford dermatologists Paul Khavari, MD, PhD and Carolyn Lee, MD, PhD have identified a UV-induced mutation in a protein active during cell division as the likely driver in tens of thousands of cases of skin cancer. Although the protein hasn’t been previously associated with cancer, the work of Khavari and Lee suggests it may actually be the most-commonly mutated oncogene in humans.

Their work was published yesterday in Nature Genetics. As we describe in our release:

Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors. They found 336 candidate genes for further study, including some familiar culprits. The top two most commonly mutated genes were CDKN2A and TP53, which were already known to be associated with squamous cell carcinoma.

The third most commonly mutated gene, KNSTRN, was a surprise. It encodes a protein that helps to form the kinetochore — a structure that serves as a kind of handle used to pull pairs of newly replicated chromosomes to either end of the cell during cell division. Sequestering the DNA at either end of the cell allows the cell to split along the middle to form two daughter cells, each with the proper complement of chromosomes.

If the chromosomes don’t separate correctly, the daughter cells will have abnormal amounts of DNA. These cells with extra or missing chromosomes are known as aneuploid, and they are often severely dysfunctional. They tend to misread cellular cues and to behave erratically. Aneuploidy is a critical early step toward the development of many types of cancer.

The mutation in KNSTRN is a type known to be specifically associated with exposure to UV light. Khavari and Lee found the mutation in pre-cancerous skin samples from patients, but not in any samples of normal skin. This suggests the mutation occurs early, and may be the driving force, in the development of skin cancers. As Khavari, chair of the Department of Dermatology and dermatology service chief at the Veterans Affairs Palo Alto Health Care System, explained in the release:

Mutations at this UV hotspot are not found in any of the other cancers we investigated. They occur only in skin cancers… Essentially, one ultraviolet-mediated mutation in this region promotes aneuploidy and subsequent tumorigenesis. It is critical to protect the skin from the sun.

Previously: Master regulator for skin development identified by Stanford researchers and My pet tumor – Stanford researchers grow 3D tumor in lab from normal cells
Photo by Michael Coghlin

Applied Biotechnology, Cancer, Genetics, Pediatrics, Research

Gene-sequencing rare tumors – and what it means for cancer research and treatment

Gene-sequencing rare tumors - and what it means for cancer research and treatment

Sequencing the genes of cancer patients’ tumors has the potential to surmount frustrating problems for those who work with rare cancers. Doctors who see patients with rare tumors are often unsure of which treatments will work. And, with few patients available, researchers are unable to assemble enough subjects to compare different therapies in gold-standard randomized clinical trials. But thanks to gene sequencing, that is about to change.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time

That’s the take-away from a fascinating conversation about the implications of personalized tumor-gene sequencing that I had recently with two Stanford cancer experts. Cancer researcher Julien Sage, PhD, is the senior author of a recent scientific paper describing sequencing of a pediatric tumor that affects only one in every 5 million people. Alejandro Sweet-Cordero, MD, an oncologist who treats children with cancer at Lucile Packard Children’s Hospital Stanford, is leading one of Stanford’s several efforts to develop an efficient system for sequencing individual patients’ tumors.

In their paper, Sage’s team (led by medical student Lei Xu) analyzed the DNA and RNA of one child’s unusual liver tumor, a fibrolamellar hepatocellular carcinoma. The cause of this form of cancer has never been found. Curious about what genes drove the tumor’s proliferation, the scientists identified two genes that were likely culprits, both of which promoted cancer in petri dishes of cultured cells. One of the genes, encoding the enzyme protein kinase A, is a possible target for future cancer therapies.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time. Sweet-Cordero is working to develop an efficient system for getting both the mechanics of sequencing and the labor-intensive analysis of the resulting genetic data completed in a few weeks, instead of the two to three months now required. “We’re trying to use this kind of technology  to really help patients,” Sage said. “If you’re dealing with a disease that may kill the patient very fast, you want to act on it as soon as possible.”

In addition to giving doctors clues about which chemotherapy drugs to try, gene sequencing gives them a new way to study tumors.

“What’s really important is that, instead of categorizing tumors based on how they look under a microscope, we’ll be able to categorize them based on their gene-mutation profile,” Sweet-Cordero said. Rather than setting up clinical trials based on a tumor’s histology, as doctors have done in the past, scientists will group patients for treatment trials on the basis of similar mutations in their tumors. “In my mind, as a clinical oncologist, this is the most transformative aspect of this technology,” he said. This is especially true for patients with rare tumors who might not otherwise benefit from clinical trials at all.

And for childhood cancers, knowing a tumor’s gene mutations could also help doctors avoid giving higher doses of toxic chemotherapy drugs than are truly needed.

“The way we’ve been successful in pediatric oncology is by being extremely aggressive,” Sweet-Cordero said. Oncologists take advantage of children’s natural resilience by giving extremely strong chemotherapy regimens, which beat back cancer but can also have damaging long-term side effects. “We end up over-treating significant groups of patients who could survive with less aggressive therapy,” Sweet-Cordero said. “If we can use genetic information to back off on really toxic therapies, we’ll have fewer pediatric cancer survivors with significant impairments.”

Meanwhile, Stanford cancer researchers are also tackling a related problem: the fact that not all malignant cells within a tumor may have the same genetic mutations, and they may not all be vulnerable to the same cancer drugs. Next month, the Stanford Cancer Institute is sponsoring a scientific symposium on the concept, known as tumor heterogeneity, and how it will affect the future of personalized cancer treatments.

Sage’s research was supported by the Lucile Packard Foundation for Children’s Health, Stanford NIH-NCATS-CTSA UL1 TR001085 and Child Health Research Institute of Stanford University. Sage and Sweet-Cordero are both members of the Stanford Cancer Institute, and the National Cancer Institute-designated Cancer Center.

Previously: Smoking gun or hit-and-run? How oncogenes make good cells go bad, Stanford researchers identify genes that cause disfiguring jaw tumor and Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers

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