Sabrina Wang

Sabrina Wang discusses her poster presentation at the AACR 2017 Annual Meeting.

Johns Hopkins undergraduate student Sabrina Wang won first place in a competition among 125 students for her research on a lethal type of pediatric brain tumor called atypical teratoid/rhabdoid tumors (AT/RT), the most common brain tumor type in infants. The award was presented at the AACR 2017 annual meeting in Washington, D.C., on April 2. Wang found that a subset of AT/RT tumors expresses a gene called MYC. Research by Johns Hopkins Kimmel Cancer Center experts has shown that cancers cells expressing this gene can alter the way they process nutrients as an energy source. In cell culture studies, Wang used so-called glutamine-inhibiting drugs to block the metabolism processes of AT/RT cells. In mice, glutamine-inhibiting drugs doubled the survival of mice implanted with AT/RT brain tumors that express MYC compared to mice with similar tumors treated with a saline control. Wang works in the laboratory of Kimmel Cancer Center pediatric oncologist Eric Raabe.

"This exciting research opens a new avenue for AT/RT treatment," says Raabe. "Glutamine metabolic inhibitors have a good safety profile in children in phase 1 studies, and we believe they may add a new, less toxic modality to AT/RT therapy. Sabrina and her lab supervisor Dr. Jeffrey Rubens have worked with dedication to bring this research to this point. I applaud Sabrina for this well-deserved recognition."

Raabe also said that this award and the scientific research that underpins it confirms undergraduate students' valuable contributions to cancer research. "Undergraduates can bring a tremendous amount of energy and enthusiasm to the lab, and Sabrina is a prime example of this," Raabe says. "She is exemplary of undergraduate students who have made major contributions to our scientific efforts."

Alex's Lemonade Stand funded the research through its Pediatric Oncology Student Training program. "This program is essential for allowing us to capture the interest of talented undergraduates like Sabrina," says Raabe.

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Jiajia Zhang was a trained oncologist in China when she read news about former Vice President Joe Biden's visit to Johns Hopkins and the launch of the Bloomberg-Kimmel Institute. "I want to make more of an impact in patients' lives, and I believe immunotherapy is the future of cancer treatment," says Zhang.

Jiajia Zhang

Jiajia Zhang

She decided to focus the rest of her career on research, and she was accepted into a master of public health program in the Johns Hopkins Bloomberg School of Public Health.

It's been a transformative year for Zhang. She plans to work with Alex Baras, M.D., Ph.D., in the Bloomberg-Kimmel Institute for Cancer Immunotherapy, to develop databases that track biological cues in patients on immunotherapy drugs that may help physicians predict their response to the drugs.

Q&A with Zhang:

When did you first hear about the launch of the Bloomberg-Kimmel Institute for Cancer Immunotherapy?
I heard about the launch of the Bloomberg-Kimmel Institute for Cancer Immunotherapy last April, shortly after its announcement. At that time, I was deciding between MPH programs in the Johns Hopkins Bloomberg School of Public Health and Harvard T.H. Chan School of Public Health. The news of the Institute really swayed my decision towards Johns Hopkins because I believe this would be the place where my aspirations would be realized - combining biostatistics and epidemiological skillsets with cutting-edge cancer immunotherapy.

What aspect of the Institute caught your interest?
Cancer immunotherapy harnesses the body's own immune system to target cancer cells. It not only has major implications for established treatments, but will also impact cancer prevention in that infectious diseases vaccines have protected hundreds of millions from viruses and bacteria. At the Bloomberg-Kimmel Institute, leading scientists collaborate closely with clinical oncologists to innovate novel immunotherapy and screening strategies to fight cancer. Its solid foundation of translational research has led to the discovery of PD-1 inhibitory receptors, development of targeted antibodies and demonstration of their clinical activity in multiple cancer types.

What area of research will you focus on in the Institute?
I hope to use what I have learned in JHSPH to help create relational databases that would link all immune analyses of immunotherapy patients to their clinical outcomes. We aspire to create platforms that can link together the information from many institutions, not only in the US but internationally. I have been fortunate to have the opportunity to initiate a relationship between Dr. Jia-fu Ji, China's most prominent gastric cancer researcher in China and director of Peking University Cancer Hospital, and Dr. Drew Pardoll, BKI director. Dr Pardoll will visit Beijing this year to discuss a collaboration that will hopefully integrate experiences with the world's largest gastric cancer population and the immunotherapy expertise of the BKI.

What do you hope your research will accomplish?
We aim to design a pathway that links scientific research and patient-level data to accelerate scientific discovery, clinical application and public change in the field of cancer immunotherapy. There are many insights on how patients will benefit from specific immunotherapies that can only come from analysis of large relational databases capturing immunologic and clinical information from hundreds, even thousands of patients.

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--This blog post celebrates the one-year anniversary of the launch of the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

When we launched the Bloomberg~Kimmel Institute for Cancer Immunotherapy last March, we committed to accelerate the progress of immunotherapies in a real and measurable way, taking advantage of its ability to produce unprecedented and durable cancer regressions. We also committed to developing “out-of-the-box” approaches that empower patients’ own immune systems to beat their cancer.

The success of immunotherapy in many cancer types now demonstrates that the immune system contains the power to vanquish virtually any cancer. The Bloomberg~Kimmel Institute has set itself apart, not just by advancing this concept through discovery but by moving beyond theory to translate these scientific discoveries into advances in the clinic and applying these advances to the treatment of patients. New technologies being developed in the Institute allow us to study immune responses in patients in ways that were unimaginable just five years ago.

It has meant the difference between life and death for a growing number of cancer patients, and it is the foundation of many new advances in cancer immunotherapy.

This progress and its impact are well-documented in publications in leading journals, such as the New England Journal of Medicine; FDA approvals of new immunotherapies; high impact collaborations and technology licensing agreements with biotech and pharmaceutical companies; and changes in the standards of cancer care. Bloomberg~Kimmel Institute clinicians and scientists have been recognized with the highest honors in the field, and the best and brightest young American and international physicians want to come here to continue their education and training.

The Bloomberg~Kimmel Institute stands out from other efforts because of its broad expertise and the foundational support that gives its experts the freedom to explore novel ideas and quickly move advances from the laboratory to the clinic. Progress flourishes in a collaborative environment that includes leading experts in essentially every field necessary to develop cancer immunotherapies and bring them to patients.

We are set up to take action, and this is evidenced in the headway made since the Institute was launched. Multiple initiatives have started that promise to bring major near-term and long-term payoffs. The energy is palpable. The number of clinical trials has exploded, side effects are now better understood and managed, research has revealed more ways cancer cells disrupt immune attacks, predictive markers of response to guide therapy have been identified, and immunology has been integrated into virtually every medical discipline, department and school at Johns Hopkins—even regenerative medicine.

Faculty members from all departments and schools at Johns Hopkins are collaborating with the Institute. Most importantly, lives are being saved.

I believe all cancer patients have an immune system capable of killing cancer cells. Our challenge is to make the immune system active against all cancers. Our experts continue to unravel the biology of the immune system and the cancer cell to make all cancers visible to the immune system and develop immunotherapies that destroy them.

Drew Pardoll, M.D., Ph.D.
Director, Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins

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*The information in this blog post is based on the webinar, “Understanding Cancer-related Cognitive Impairment,” hosted by the Kimmel Cancer Center's Breast Cancer Program.

Q: What type of cognitive assessments can be done for cancer patients undergoing treatment or who have completed treatment who complain about ‘chemo brain’?

A: Tracy Vannorsdall, Ph.D., a neuropsychologist at JohnBrain_webs Hopkins in the Division of Medical Psychology, says her assessments usually require a three- to four-hour appointment. “I will review a patient’s medical records, and spend an hour taking a medical history while focusing on issues such as stress, sleep, mood, and in what kinds of situations the patient notices cognitive difficulties.” One of her technicians provides formal, one-on-one cognitive testing designed to look at different thinking skills, such as the ability to pay attention, to think quickly, to remember, to plan and to reason and problem-solve. Then patients fill out questionnaires that address mood, stress, sleep and fatigue.

“I pull it all together and look at the pattern of strengths and weaknesses in terms of cognition – where do we expect a patient to be based on his/her age and background, where the person is doing well and where he or she is experiencing difficulties,” Vannorsdall adds. “I like to craft a tailored, research-supported intervention using a person’s cognitive strengths to help counteract their cognitive weaknesses. Sometimes that involves keeping diaries to track cognitive errors and their context, sometimes I need to refer patients on to additional providers for treatment for depression and anxiety or sleep difficulties. I work with patients to address all of the potential modifiable factors to improve cognition and can help get them moving toward where they want to be. I can also help patients returning to work to make appropriate requests for accommodations. Employers often want to help employees be as successful as possible.”

Neuropsychological evaluations may be less frequently available in rural settings but there are psychologists, social workers, and other mental health providers who are knowledgeable about complex medical issues and the contributing factors to cognitive difficulties, Vannorsdall says. Quite often, the service is covered by insurance.

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Immunotherapy_Cancer_Tcells_iStock-486569692

T-cells attacking a tumor cell

A decade ago, Suzanne Topalian, M.D., led a team of researchers who made an astonishing contribution to how cancer is fought. Many cancers can “put the brakes” on the body’s immune cells — cells that would normally storm into a tumor and destroy it. Topalian, director of the Melanoma Program at the Johns Hopkins Kimmel Cancer Center and associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and others developed a class of drugs called immune checkpoint blockers, which take the brakes off the immune system and give it a chance to fight back against cancer.

“Now, every oncologist is engaged in immunotherapy. These drugs are becoming a common denominator for cancer therapy,” Topalian says.

But as the drugs are approved for more types of cancer and used by more patients, oncologists still have questions they want to answer about cancer immunotherapy, says Topalian.

Which patients will respond best? Scientists are in the midst of a huge hunt for biomarkers — which can be anything from genetic mutations to proteins sampled from tissue or blood — that can help them determine which patients are most likely to benefit from immunotherapies, such as checkpoint blockers. There are some cancer treatments that target single genetic mutations, “but immunotherapy biomarkers are a bit more complex than that” and could involve a number of genes and proteins, Topalian says.

Johns Hopkins researchers have played leading roles in searching for these biomarkers, she says. For instance, in 2015, a team of Johns Hopkins oncologists found genetic biomarkers that identified a small group of colon cancer patients who responded well to a checkpoint blocker. “We need more sensitive and more specific markers like this to help us learn which patients are most likely to do well with these treatments,” says Topalian.

Can we combine immunotherapy with other treatments? “We know from lab studies that some of these checkpoint blocker therapies are potent, but they’re even more powerful when you combine them with other drugs,” Topalian notes.

Numerous clinical trials at Johns Hopkins and elsewhere are testing these combinations, whether adding a standard therapy, like radiation or chemotherapy, to a checkpoint blocker or combining an immunotherapy drug that lifts the brakes from the immune system with another drug that revs up the immune system. In some trials, Topalian says, both of the drugs could be still be experimental, “which is a new frontier for drug development.” The hope, she says, is that drug combinations that contain some kind of immunotherapy could extend the success of these drugs in difficult-to-treat cancers, like metastatic pancreatic, prostate, and head and neck cancers.

Can we improve how we deliver cancer immunotherapies? For the moment, checkpoint blockers are given to patients intravenously every two to three weeks during an hourlong treatment. But Topalian says scientists are studying whether this is really the best way to give these drugs, or if there might be a way to deliver them as a pill or in a form that requires less frequent clinic visits.

As more patients begin to benefit from these drugs, she notes, “We’re also doing active research to find out how long we can or should keep administering these drugs to patients, whether it’s months or years or indefinitely.”

What more can we tell patients about these treatments? “I think people are fairly well-informed about this, but it’s important to remember that this is a different kind of therapy because it doesn’t directly kill tumor cells,” Topalian explains. “This therapy treats the immune system, and then the immune system attacks cancer cells.”

Patients may worry about side effects from immunotherapy, especially whether the treatment will cause their immune systems to attack normal, healthy tissue. “Most of the side effects that we see are mild and managed fairly easily,” such as fatigue or rashes, says Topalian.

Topalian also wants patients to know that the work on immunotherapies — even ones that are already being used to treat cancer — never stops. “We study these drugs in patients and then in the lab and then back again to better understand how they are working,” she says. “For patients with cancer, I think there’s more reason than ever to be hopeful.”

 

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*The information in this blog post is based on the webinar, “Understanding Cancer-related Cognitive Impairment,” hosted by the Kimmel Cancer Center's Breast Cancer Program.

Q: What can I do to improve my cognition during and after cancer treatment?

A: Use areas of cognitive strength to compensate for any weaknesses, advises Tracy Vannorsdall, PhD, a neuropsychologist at Johns Hopkins in the Division of Medical Psychology. “You may have to do things a bit differently, and it takes work to create new habits,” she says. “Make things a habit whenever you can -- research shows habits are more deeply ingrained and resilient than telling yourself to remember things.”

For example, she says, leave your keys, cell phone and wallet by your front door. Have a routine every night to get ready for the next day so you don’t have to stop and think things through. Vannorsdall also recommends the following tips:

1. Pay attention and become an active listener. Remind yourself to pay attention; stop every few minutes when listening to someone talk or to a lecture and notice if your mind has wandered. If you meet someone new, say their name to yourself five times and use it when you say good-bye. When taking notes, take them in your own words and process them so you’re encoding them deeply. Make new information as rich as possible – think in multiple senses and think of where you were when you learned something new.

“Learning and memory is like a file drawer,” Vannorsdall says. “You really have to attend to what is going in and organize it so you can pull out the information you need later.”

2. Give your memory a rest. Use memory aids – take notes, use index cards to write things down, create detailed calendars, use smartphone applications/apps, take photos or leave yourself voice messages. Become an active reader using the PQ4R method: preview the material, ask yourself questions, read it, reflect on it, recite answers to your questions, review what you’ve just done. Review your day before falling asleep at night. Memories become stronger and more permanent when you pull them up and review.

3. Set yourself up for success. “Multitasking is difficult,” Vannorsdall says. “Limit yourself to one activity at a time. Make a list of what you want to do or break down the steps in a large task, pick one task, and work on and complete it before moving on.” Minimize distractions -- get materials together, work in a quiet area or use a white noise machine, turn off alarms for email or social media; and give yourself plenty of time. Take breaks as needed so you stay fresh.

4. Stay mentally active. There is no one magic activity but diversity and novelty are important. Do new things to keep your brain healthy. “Like with physical exercise, where your body acclimates and needs to be pushed harder, our brains adjust, too,” Vannorsdall says. Socialize, play card games, take a class, do puzzles, or go for walks in new neighborhoods.

5. Eat a healthy diet and exercise. Walking and low-impact exercise like yoga, Qigong, and Tai Chi have been shown to improve thinking speed, memory, executive functioning, and improvement in quality of life in as little as one month, Vannorsdall says. Exercise can also decrease fatigue and improve stress.

6. Get good sleep. “Fatigue is a major issue in those being treated for cancer,” Vannorsdall says. “It’s closely tied to one’s degree of distress.” There is good evidence that memories are consolidated during sleep, and adults need six hours of natural sleep to make stable memories. Sleep medications can interfere with natural sleep patterns, she says. Keep a regular schedule for meals, medications, and exercise. Avoid naps, caffeine after lunch and alcohol within six hours of bedtime. Don’t smoke before bed or be too hungry or too full. Avoid strenuous exercise before bed. Establish rituals to help you relax each night, and don’t go to bed unless you are sleepy. Keep your bedroom quiet, dark and cool.

7. Learn how to manage stress. Cancer treatment can be stressful, between a person’s reaction to the diagnosis, managing treatment challenges and its impact on work and family life, Vannorsdall says. Deep breathing exercises or progressive muscle relaxation can help.

8. Pursue treatment. Some patients benefit from psychotherapy or supportive counseling, medications, or formal cognitive rehabilitation programs, where you attend a session once or twice a week and learn tools to use at home. Start a diary or log to track your cognitive problems – When do they occur? In what settings? This can give you a sense of when you do well or when you need additional help, Vannorsdall says.

 

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More than 20 years ago, when Johns Hopkins scientists Bert Vogelstein, Ken Kinzler and their colleagues linked certain cancers to mutations in genes that repair DNA, they may not have imagined that their findings would spark an idea that has become a crystal ball for predicting whether immunotherapy is more likely to work in a person with cancer.

The idea, featured in the American Society of Clinical Oncology's Clinical Advances 2017, began four years ago at a meeting between Vogelstein and scientists at the Bloomberg~Kimmel Institute for Cancer Immunotherapy to figure out why a single patient with colon cancer had responded to an immunotherapy drug and 15 others with colon cancer had not. What was different in that single patient? The scientists had a hunch that tumor cells in the lone responder had more mutations than those of the other patients. More mutations trigger the production of more abnormal proteins, which appear foreign to the immune system. These mutation-ridden tumor cells are more visible to the immune system than tumors with fewer mutations, and immunotherapy may be much more likely to work in these patients.

The hunch paid off, and when the scientists sequenced the patient's tumor, they found mutations in a set of genes, called "mismatch repair," which work to mend DNA mistakes. Bloomberg~Kimmel Institute scientists organized a clinical trial of patients with and without mismatch repair mutations and presented and published initial results in 2015. The trial was expanded and more results were presented in 2016 showing high response rates to the immunotherapy drug pembrolizumab among patients with many types of cancer who carry mismatch repair mutations. Bloomberg~Kimmel Institute experts estimate that 20,000 new patients who carry mismatch repair mutations are diagnosed each year in the U.S.

One of those patients is Stefanie Joho. Given a death sentence and no hope, Stefanie came to Johns Hopkins looking for a therapy that could buy her time. She enrolled in the Bloomberg~Kimmel Institute clinical trial and is now in complete remission. Listen to Stefanie's experience with immunotherapy:

 

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On a block of vacant row homes near the Johns Hopkins Medicine campus in East Baltimore, the Ulman Cancer Fund is building an 8,000 square-foot residence for young adults being treated for cancer. It will serve as a "home away from home" for people 15 to 39 who come from a distance to be treated at either the Kimmel Cancer Center or University of Maryland Greenebaum Cancer Center. Kenneth Cooke, M.D., director of bone marrow transplant at the Kimmel Cancer Center says, "it will be a place where our patients can rest and re-energize; where they can educate, motivate and support one another; where they can laugh and cry without batting the eye of a passerby; where they can shout out in anger or in joy; where they can celebrate or be comforted."

Kimmel Cancer Center patient Karen Sollenberger spoke at the groundbreaking event for the Ulman Fund's new residence and was featured in an interview with WBAL-TV. The Baltimore Sun also reported on the new residence, featuring comments from Dr. Cooke.

Listen to Dr. Cooke speak about issues facing young adults with cancer:

 

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AACR Cancer Screening Guidelines WebinarWhat cancer screenings do I need and when? If this answer isn't clear to you, listen to Kimmel Cancer Center director William Nelson moderate a webinar on "Making Sense of Cancer Screening Guidelines," hosted by the American Association for Cancer Research and Cancer Today magazine. Nelson and his co-panelists will summarize the guidelines and provide their perspectives so that you can make informed choices with your doctor. Register today at www.aacr.org/webinar.

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The Johns Hopkins Greenberg Bladder Cancer Institute recently announced a joint effort with the Bladder Cancer Advocacy Network (BCAN) to fund up to two awards totaling $100,000 for young scientists. As part of the announcement, the Institute's director, David McConkey, Ph.D., gave us his thoughts on recent bladder cancer advances and ongoing research.

Recent advances, says McConkey, include the FDA approval of the immunotherapy drug atezolizumab for bladder cancer patients whose disease worsens after receiving chemotherapy. Scientists have recently charted the genomic characteristics of some rare bladder tumors, in addition to muscle-invasive and nonmuscle-invasive bladder cancers. Such characterization helps create a genomic blueprint of these cancers to help pathologists more easily identify them. The blueprints, says McConkey, also give scientists clues to the behavior of certain tumors, sorting out which ones may be more aggressive and need different therapies.

McConkey says that bladder cancer scientists also are working to identify genetic characteristics of patients who may be cured by chemotherapy alone, potentially avoiding surgery to remove the bladder. He expects that other immunotherapy drugs that work through the same mechanisms as atezolizumab may soon be approved by the FDA to treat bladder cancer, and scientists are looking for genetic or molecular characteristics of patients more likely to respond to them.

 

 

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