Posted tagged ‘cancer’

Stanford chemists produce chemical — originally from marine creature — needed for new drugs

October 16, 2017

One person’s weed is another’s flower. A good example of this is spiral-tufted bryozoan, an invasive marine organism that fouls up marine environments. Although considered a pest by many, spiral-tufted bryozoan is much sought after by researchers since it can produce biostatin 1 — a chemical critical to the development of promising new drugs to treat HIV/AIDS, Alzheimer’s disease and cancer.

Although this bryozoan is abundant, bryostatin 1 is very scarce because it’s difficult to harvest from the sea creature and complex to synthesize. In fact, the National Cancer Institute’s stock of bryostatin 1 is nearly depleted from supplying over 40 clinical trials. So Stanford chemists have developed a new, easier way to synthesize bryostatin 1, as recently reported in Science.

Paul Wender, PhD, a professor of chemistry and of chemical and systems biology at Stanford, has been working for years to develop bryostatin analogs that are more effective for drug development. However, the dwindling supply of bryostatin 1 inspired him to synthesize the drug itself.

“Ordinarily, we’re in the business of making chemicals that are better than the natural products,” Wender said in a recent Stanford news release. “But when we started to realize that clinical trials a lot of people were thinking about were not being done because they didn’t have enough material, we decided, ‘That’s it, we’re going to roll up our sleeves and make bryostatin because it is now in demand.’”

The researchers devised a much simpler synthesize process, cutting the steps down from 57 to 29. They also dramatically increased the yield, making it tens of thousands of times more efficient than extracting bryostatin from spiral-tufted bryozoan and significantly more efficient than the previous synthetic approaches. And they confirmed with a wide range of tests that their synthetic bryostatin was identical to a natural sample supplied by NCI.

So far, the team has produced over two grams of bryostatin 1, and a single gram can treat about 1000 cancer patients or 2000 Alzheimer’s patients, according to their paper. After scaling up production, they expect manufacturers to produce about 20 grams per year to meet clinical and research needs, Wender said in the news release.

They also expect their work could facilitate research using bryostatin analogs derived from their synthesis process. The paper explains that these analogs “are proving to be more effective and better tolerated in comparative studies with cells, disease models in animals, and ex vivo samples taken from HIV-positive patients.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Detecting single cancer cells with light: A podcast

July 13, 2017

Photo by Burak Kebapci

When cancer is spotted early, it’s much easier to thwart. So researchers, including Stanford’s Jennifer Dionne, PhD, are working to detect cancer more effectively. Dionne, an associate professor of materials science and engineering, is developing a nanomaterial-based probe that may be able to detect a single cancer cell.

She described her work in a recent episode of the Future of Everything radio show, hosted by Russ Altman, MD, PhD, a Stanford professor of bioengineering, of genetics, of medicine and of biomedical data science.

“What our lab is trying to do is create light-emitting nanoparticles that change their color when there is an applied force on the nanoparticles. So that way we can make mechanical forces visually perceptible,” she explained to Altman. These nanoparticle already change color in response to the tiny forces generated by cells and groups of cells, she said, and cancer cells are known to exert more force on their environment than healthy cells.

Dionne explained: “Generally a cancer cell wants to take up a lot of nutrients and it’s basically growing and dividing more quickly than a healthy cell. You can imagine given the speed of replication that it’s going to exert a higher force on its environment than a healthy cell. So our nanoparticles offer the ability to detect even a single cancer cell based on the forces that that cancer cell is exerting on its environment.”

That could help pathologists spot abnormal cells in a biopsy sample, she said. “This could be a really cool in vitro probe of whether or not in a biopsy [sample] you have even one cancer cell, which you can tell just by looking at the color the nanoparticles are emitting,” she told Altman.

Although their primary focus was on the development of nanomaterials with energy and biomedical applications, the conversation did take a few interesting twists. I particularly enjoyed their discussion on the design challenges behind making a Harry Potter invisibility cloak. Hint: Like water waves flowing around a rock, you need to create a cloak that allows light waves to flow smoothly around the hidden object so they emerge on the other side as if they hadn’t passed through the object — it’s difficult, but they’re working on it.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Mowing down cancer: A podcast featuring Stanford chemist Carolyn Bertozzi

May 23, 2017

To explain her work, Stanford chemistry professor Carolyn Bertozzi, PhD, often turns to analogies. Cancer cells, she says, are like M&Ms with a hard sugar coating. As she recently explained on the “Future of Everything” radio show, the coating’s function has remained a mystery for years, but now researchers are making real progress.

“We have come to think of these sugars as kind of a 2D barcode. The patterns are different on different cell types, and yet all of the cells of a certain type have a common pattern,” Bertozzi told show host Russ Altman, MD, Phd. “So there is a code there, but we don’t quite have the means to scan it and we don’t yet understand it.”

So what do the barcodes look like on cancer cells? Bertozzi describes them as a superposition of two barcodes — the original cell’s barcode and a new cancerous one. And the cancerous barcode looks similar for many different cancers. Researchers have found that these sugar barcodes on cancer cells can promote disease progression by turning off the immune system. “They basically tell immune cells, ‘There’s nothing to see here. Move along. I’m perfectly fine and healthy,’” Bertozzi said.

Using an analogy, she explained in the podcast that the cancer cells put on makeup to look fabulous and mesmerize the immune system, fooling it into thinking that the cells are healthy so the cancer can progress unimpeded. Her lab is developing a way to strip off this makeup.

Her team has developed a way to use enzymes to cut off the sugars, making the cells available for immune cells to target. She explained: “They were enzymes that normally play a role in digesting sugars. So what we’ve done is repurposed these enzymes so we can target them right to the surface of the cancer cell. And literally they’ll just go across the surface of the cell mowing off the sugars, like stripping off the makeup. And then the cells can be seen for what they truly are.”

Bertozzi is also involved in a company that hopes to bring this “lawn mower” technology to the clinic within the next two years, but they first need to get good preclinical data as proof-of-concept. The company is currently focused on developing new treatments for breast, lung and kidney cancers.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Computer algorithm predicts outcome for leukemia patients

February 22, 2017
Image by PeteLinforth

Image by PeteLinforth

Researchers have developed a machine-learning computer algorithm that predicts the health outcome of patients with acute myeloid leukemia — identifying who is likely to relapse or go into remission after treatment.

Acute myeloid leukemia (AML) is a cancer characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells.

A standard tool used for AML diagnosis and treatment monitoring is flow cytometry, which measures the physical and chemical characteristics of cells in a blood or bone marrow sample to identify malignant leukemic cells. The tool can even detect residual levels of the disease after treatment.

Unfortunately, scientists typically analyze this flow cytometry data using a time-consuming manual process. Now, researchers from Purdue University and Roswell Park Cancer Institute believe they have developed a machine-learning computer algorithm that can extract information from the data better than humans.

“Machine learning is not about modeling data. It’s about extracting knowledge from the data you have so you can build a powerful, intuitive tool that can make predictions about future data that the computer has not previously seen — the machine is learning, not memorizing — and that’s what we did,” said Murat Dundar, PhD, associate processor at Indiana University-Purdue University, in a recent news release.

The research team trained their computer algorithm using bone marrow data and medical histories of AML patients along with blood data from healthy individuals. They then tested the algorithm using data collected from 36 additional AML patients.

In addition to being able to differentiate between normal and abnormal samples, they were able to use the flow cytometry bone marrow data to predict patient outcome — with between 90 and 100 percent accuracy — as recently reported in IEEE Transactions on Biomedical Engineering.

Although more work is needed, the researchers hope their algorithm will improve monitoring of treatment response and enable early detection of disease progression.

Dudar explained in the release:

“It’s pretty straightforward to teach a computer to recognize AML. … What was challenging was to go beyond that work and teach the computer to accurately predict the direction of change in disease progression in AML patients, interpreting new data to predict the unknown: which new AML patients will go into remission and which will relapse.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

New blood test could detect early-stage pancreatic cancer

February 17, 2017

Pancreatic cancer is one of the leading causes of cancer death, because it is seldom detected before the disease has spread to other organs. Only 8 percent of people with pancreatic cancer survive five or more years after diagnosis.

Now, researchers hope to change this bleak scenario with an improved blood test that can detect early-stage pancreatic cancer. A multi-institutional team led by Tony Hu, PhD, an associate professor at Arizona State University, recently reported on their results in Nature Biomedical Engineering.

The researchers first identified the presence of a protein in the blood, called ephrin type-A receptor (EphA2), which is overexpressed by pancreatic tumors. Next, they developed a biosensor using gold nanoparticles that selectively bind to EphA2, changing their light emitting properties. This allowed the team to quantify the amount of EphA2 in a blood sample to see if it is overexpressed.

They validated their biosensor in a pilot study involving 48 healthy people, 59 patients with stage I-III pancreatic cancer and 48 patients with chronic pancreas inflammation. The later condition is often confused with pancreatic cancer using existing diagnostic tests like ultrasound.

The biosensor was able to accurately identify the patients with pancreatic cancer — even those with early stage disease — as well as the patients with chronic pancreas inflammation. If these results are validated with a larger clinical trial, the blood test could screen for pancreatic cancer and could be adapted for other diseases.

“We are now working on lung cancer and lymphoma and have very positive results,” Hu said in a recent news story. “In addition to cancer, we are conducting a project on tuberculosis diagnosis. Theoretically this test could be applied to any type of disease.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Cancer clinical trials: Stanford strives to enroll more diverse participants

January 4, 2017
Image by geralt,

Image by geralt

In a previous post, I described why I enrolled in a clinical trial at Stanford to treat my Hodgkin’s lymphoma. But I didn’t share the result: I received radiation therapy and chemotherapy — instead of the standard treatment of exploratory abdominal surgery — and I’m confident it helped me to be cancer free for the last 20 years.

However, my experience was unusual: Very few cancer patients participate in clinical trials and many aren’t even aware that they qualify for one. In order to advance cancer research, more participants are needed — especially ethnic and racial minorities who are vastly underrepresented in clinical trials. This is particularly important for diseases that occur more frequently or appear differently in non-white populations. For example, African American women have a 41 percent higher mortality rate for breast cancer than white woman, despite having a lower incidence rate, but only about 5 percent of clinical trial participants — for all diseases — are African American.

The Stanford Cancer Institute (SCI) knows this problem well.

“A key way participants learn about our cancer clinical trials is through physician referrals,” said Rachel Mesia, community engagement manager at SCI. “Physicians and oncologists practicing at Stanford educate their patients about clinical trials. They also network with physicians from other health-care practices to prompt them to make referrals.”

Participants also find Stanford cancer clinical trials through SCI’s clinical trials information service, which directs callers to an English- or Spanish-speaking outreach specialist who provides general clinical trials information and links callers to study coordinators.

Similarly, Mesia said SCI’s website and mobile app make it easier for patients to locate clinical trials that match their medical conditions using patient-friendly word searches. The mobile app will be updated in January to add new features.

“I’ve heard from many sick patients that they don’t have the energy to constantly go onto a search engine to see if any new clinical trials have opened up,” said Sarah Pelta, SCI’s communications manager. “That’s why were putting push notifications into our mobile app, as well as the ability to sign up for email notifications. So patients can just receive an email when a trial opens up that matches their search parameters.”

Also key to successful recruitment is the inclusion of stories from past clinical trial participants to help make a human connection. “From our website analytics and from speaking to patients, we know that patients really want to see what other patients are experiencing. So we’ve added patient photographs and videos to our website,” Pelta said.

SCI tackles the challenge of minority recruitment by reaching out to particular communities, in part by distributing information at community health and cancer patient events, Mesia said. “We also partner on educational presentations with a variety of community organizations, such as cancer support groups, social service organizations and churches,” she said. “And we participate in some ethnic-specific media interviews, including television, radio and newspapers.”

In addition, SCI has interactive kiosks dispersed throughout their cancer centers that provide basic clinical trials information and a search tool — in English, Spanish, Chinese and Russian.

Over the last six years, SCI has also held a Cancer Clinical Trials Awareness Week event to further increase visibility. In April 2017, this will be expanded to a month-long event highlighting genomics, immunology and other targeted approaches to cancer. Everyone is invited, and they’re planning to make the talks available online to expand access, Mesia told me.

The SCI has adequate participation overall, but they are still struggling to recruit minorities. “Currently our greatest disparity lies amongst the African American population,” Mesia said. “We’re doing okay with African Americans who are existing cancer patients at Stanford, but there is an issue when we look at our catchment area as a whole.” One barrier is that fewer African Americans live near Stanford’s cancer centers, and those living in more distant Bay Area counties have significant commute challenges, she said. “The reality is that some people’s personal lives make it unfeasible to be part of a Stanford clinical trial.”

But that just means the SCI staff need to work even harder. “We need social and health equity for all populations who are getting cancer,” Mesia said.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Cancer clinical trials: Why I chose to participate, but so many others don’t

January 2, 2017
Photo by geralt

Illustration by geralt

When I was 29 years old, I was one of the healthiest people I knew. I biked 10 miles to work, played ultimate frisbee, slept at least eight hours each night and ate nutritious, organic food. And then I found an enlarged lymph node in my neck.

My life suddenly became a whirlwind of doctor appointments and diagnostic tests: chest X-rays, blood tests, CT scans, a lumbar puncture, lymph node biopsy and a lymphangiogram. The tests showed another enlarged lymph node near my heart, and I was diagnosed with stage IIA Hodgkin’s lymphoma.

Unbelievably, I had cancer. I was faced with scary medical decisions that could impact both my survival and fertility. How do you make those kinds of decisions? As a scientist, I immediately started researching Hodgkin’s and talking to medical experts.

According to my physician, the standard treatment for stage II Hodgkin’s entailed exploratory abdominal surgery in order to biopsy my organs and check for further signs of the disease, as well as removal of my spleen. This would be followed by radiation therapy to my chest and neck.

Most people choose the standard treatment — it’s the gold standard for a reason, right? However, I wasn’t convinced that I wanted the surgery, because my diagnostic tests showed no sign of the disease below my diaphragm. I didn’t want to unnecessarily lose my spleen, which plays a vital role in the immune system by filtering blood and fighting certain deadly bacteria.

Luckily, my physician recommended another treatment option: a Hodgkin’s clinical trial at the Stanford Cancer Institute. This phase III clinical trial was testing whether a specialized chemotherapy cocktail was more effective at treating stage II Hodgkin’s than the standard abdominal surgery, and the investigators’ previous clinical trials had shown excellent results with similar chemotherapies.

So I struggled with whether I wanted radiation therapy combined with exploratory surgery or chemotherapy — both were scary and both would have long-term side effects. However, it wasn’t really my decision. I could only decide whether or not to enroll in Stanford’s clinical trial, and then the treatment option would be randomly selected for me. Eventually I decided I could live with this lack of control, because both treatments were going to be effective.

People typically participate in a clinical trial to “advance medicine” or “improve the lives of others,” according to the Center for Information and Study on Clinical Research Participation. While I was happy to contribute to scientific research, I enrolled in the clinical trial for myself — to get the best care. I knew that other study participants came from across the world to Stanford since it was one of the premier places for Hodgkin’s treatment, and I lived just five miles away.

I was fortunate in many other ways as well; I had personal health insurance. I also had flexible hours as a research scientist and could work full-time during treatment, so I didn’t have financial worries. In addition, I was used to communicating with doctors as peers, so I didn’t fear being a ‘guinea pig.’

These types of barriers — limited access to trials, financial concerns and trust issues — prevent many people from participating in clinical trials. Nationwide, only about 3 percent of adults with cancer participate in clinical trials. As a result, about 40 percent of all oncology clinical trials fail to meet their minimum patient enrollment, which has a major impact on cancer research.

Researchers use many tactics to attract trial participants. In an upcoming post, I’ll share what I learned about Stanford’s efforts to boost the enrollment of minorities in its oncology clinical trials.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.


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