In part one of this series, experts at the Johns Hopkins Kimmel Cancer Center discussed their predictions for the future of cancer medicine during a Cancer Conversations forum on Nov. 3, 2015. These experts also discussed how they collaborate with other scientists. On the panel were:

  • Kimmel Professor and Director of Radiation Oncology and Molecular Radiation SciencesTheodore DeWeese,
  • Kimmel Scholar and GI cancer pathologist Laura Wood,
  • Kimmel Scholar and cancer biology cell division scientist Andrew Holland,
  • Martin D. Abeloff Scholar in Cancer Prevention and Control and Deputy Chair in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health Elizabeth Platz,
  • Co-Director of Cancer Immunology Charles Drake, and
  • gene sequencing expert Vasan Yegnasubramanian.

Collaborations Informing Cancer Research and Medicine

Platz:  The amount of methylation of DNA is critical to whether a gene can produce a protein or not—whether that gene is active or inactive.  I am collaborating with Vasan to study methylation patterns in individuals. One unique study came about through a Kimmel Cancer Center partnership with Howard University. We have developed a repository for umbilical cord blood to explore differences in methylation patterns to see if it may help explain why African American men have much higher risk of prostate cancer than white men.  Could there be underlying molecular changes in methylation patterns that begin very early in life and set people up for cancer later in life?

Drake:  We have a depth of expertise here in epigenetics and I am collaborating with experts to better understand immune responses to cancer. Perhaps some immune responses are being blunted by epigenetic mechanisms and we could develop drugs to target this.

Wood: We need to become more specific about what the cells we analyze. Tumors are a mix of tumor cells, immune cells and other cells. I’d like to expand the understanding of cancer biology to get a good read on what is happening within a tumor so that we may identify precursers that will allow us to detect cancer earlier and even prevent it.

Holland:  Cancer research has been empowered by new instruments that allow us to peer inside the living cell and see things happening with exquisite detail. In the laboratory, we can use them to manipulate the genome, change the genetic content of these cells, to see how it changes the physiology of these cells.

DeWeese:  Why do cells of different types respond differently to radiation therapy when they have the same DNA? Cell biology, using a biomedical engineering perspective may shed light on the biomechanics of how these cells are organized and how this dictates how they respond to therapy. If we can understand how structure influences how cells respond, there are things we can do to manipulate this structure and ultimately response to treatment.

Cancer is an evolutionary process. If we explore the things that we know can wipe out a species—changes in temperature, pH, and oxygen content—can we adapt evolutionary biology into cancer therapies? Can we use new technologies, for example, to alter the temperature in the microenvironment and stress cancer cells into death?

Yegnasubramanian: Computer science and engineering is key.  What we have learned about cancer through gene sequencing is exceeding our ability to analyze it. Within a decade, we will need innovations to store and process our genomic data with computing technology. How do we address this challenge and continue to make advances as we simultaneously work toward innovations that address these challenges?

Watch the forum:

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On Nov. 3, 2015, a capacity crowd of more than 250 Johns Hopkins leaders, faculty, staff, students, donors, and other guests filled the Albert H. Owens Auditorium at the Johns Hopkins Kimmel Cancer Center to honor the philanthropy of Sidney Kimmel for advancing cancer discovery and care. Hundreds more watched via video streaming as Kimmel Cancer Center Director William Nelson led a thoughtful discussion of challenging topics in cancer medicine and research by a panel of cancer experts, including Kimmel Professor and Director of Radiation Oncology and Molecular Radiation Sciences Theodore DeWeese; Kimmel Scholars, GI cancer pathologist Laura Wood and cancer biology Panel of experts at the Johns Hopkins Kimmel Cancer Centercell division scientist Andrew Holland; the Martin D. Abeloff Scholar in Cancer Prevention and Control and Deputy Chair in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health Elizabeth Platz; Co-Director of Cancer Immunology Charles Drake; and gene sequencing expert Vasan Yegnasubramanian.

The experts shared their views on several topics. The following are their opinions on what the future holds for cancer medicine. In two upcoming blogs, we'll share how these scientists are collaborating with others and the questions that "keep them up at night."

The Future of Cancer Medicine

Laura Wood, cancer pathologist: I hope to improve our ability to use pathology to figure out what treatment will help each patient.  There will never be one cure for everyone but rather different cures for different patients. This is what we call precision medicine. We need to continue to use pathology to divide cancers into smaller and smaller subsets to help decipher who will respond best to what therapy.

Andrew Holland, cell division researcher: Cancer is disregulated cell growth. If we understand more about the molecular differences between how normal cells divide and cancer cells divide, we can develop therapies that target cancer cell division and leave normal cells untouched.

Elizabeth Platz, cancer epidemiologist:  I envision ways we can intervene in cancer, beyond treatment, to prevent poor outcomes. We need to identify subsets of people who are likely to benefit more from specific strategies.  As we understand the biology of cancer better, we may be able to figure out better ways of using prevention strategies for people who have cancer and those who do not. For example, smoking is linked to cancer among the general population, but it is also a risk factor for poor outcomes in patients who already have cancer.

Charles Drake, cancer immunologist: Some cancers are recognized by the immune system and immune therapy—using the immune system to fight the cancer—should be a first line therapy for these patients. Some patients have tumors that don’t readily respond to immune approaches, and for these patients we’ll need to develop combinations of radiation and conventional therapies along with immune therapies to have an impact.

Ted DeWeese, radiation oncology expert: We will expand our use of sophisticated data warehouses that have patient history, physical exam, imaging, laboratory studies, and genetic information embedded in them along with structured information on treatment outcomes and related side effects. We have built such a system in radiation oncology that analyzes any treatment plan and adjusts it to create an optimal plan that maximizes therapeutic benefits and minimizes side effects. It has already been deployed at the Kimmel Cancer Center and is now being expanded nationally, in Canada and Japan. The world of oncology changes when we have millions of patients to reflect upon to devise the best treatment for every individual patient.

Vasan Yegnasubramanian, gene sequencing expert:  Many of the problems we face today can be addressed through a convergence of technologies. Sequencing and the data it provides is revolutionizing how we make treatment decisions. There is an immense depth of information we can harness, but we need to figure out how best to gather it and how best to use it.

Watch the Conversations on Cancer forum: 

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The Johns Hopkins Kimmel Cancer Center joined all of the nation's cancer centers designated by the National Cancer Institute in endorsing human papillomavirus (HPV) vaccination to prevent cancers caused by the ubiquitous virus.

HPV infections are known to cause most cervical, anal, oropharyngeal and other genital cancers. Vaccines are available to prevent infections of certain strains of HPV and are recommended by the CDC for boys and girls at ages 11 or 12 years.

However, vaccination rates remain low in the U.S. The published statement reflects the Cancer Centers' message to parents, adolescents and health care providers about the importance of HPV vaccination.

NCI_HPV_Consensus_Statement_012716

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Yesterday's announcement from the United States Preventive Services Task Force of its final recommendations on breast cancer screenings was met with disagreement from many doctors who specialize in breast imaging. Dr. Susan Harvey, director of Breast Imaging at Johns Hopkins joined others who said the announcement will not change their own practices.

"What this controversy has brought to light is the urgent need for us to demonstrate how modern breast cancer screening is cost effective, scalable, saves lives and equally valuable to a woman in her 60s as well as her 40s, where breast cancer caught early has a lasting impact in costs to society and our workforce," says Harvey.

Read more information from Johns Hopkins experts discussing breast cancer screening:

  • Breast cancer screening controversy: expert Susan Harvey authored this op-ed in April with her take on the topic.
  • Breast Imaging director Susan Harvey discusses mammography and tomosynthesis in this video.
  • Watch a video on "What you need to know about Screening Mammography."

 

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***This post was written by the Kimmel Cancer Center's Chief Administrative Officer, Terry Langbaum, in memory of Ellen Stovall, late president of the National Coalition for Cancer Survivorship, who died Jan. 5.  

The first time I met Ellen Stovall, we immediately felt that we had known each other for years. We had so much in common -- our mutually shared medical histories, yes, but much more importantly, our mutual determination to make life better for cancer patients and cancer survivors. Ellen used all of her resources to make a difference in the lives of cancer survivors, and did she ever have resources. She was intelligent, determined, articulate, endlessly energetic, genuine, and intuitive. She was comfortable with medical professionals of the highest order, political leaders at the national level, cancer advocacy professionals, patients and caregivers. In the National Coalition for Cancer Survivorship, she was able to create and build an advocacy organization that filled a gap by recognizing and giving voice to so many individuals experiencing the late effects of cancer treatment, including chronic pain, chronic anxiety, some pretty awful co-morbidities caused by cancer treatment, and the very real risks for secondary cancers in those who have had cancer treatment. Until her last day, Ellen continued to do what she passionately loved. I hope I am that fortunate. Today, cancer researchers work tirelessly to find treatment protocols that cure the cancer, but that reduce the late health risks associated with cancer treatment. In no small part, this is a result of Ellen Stovall's life's work. We can all honor her memory by continuing her legacy.

Terry S. Langbaum
Chief Administrative Officer
Kimmel Cancer Center at Johns Hopkins

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The following response was provided by Drs. Cristian Tomasetti and Bert Vogelstein in regards to a new paper published in the journal Nature:

Scientific debate on the factors responsible for cancer is a welcome and important part of solving the challenges we face in reducing the burden of this disease . The differences between our conclusions and those of Hannun et al. are dramatic. Through re-evaluation of our data, the authors conclude that virtually all forms of cancer are the result of extrinsic factors (Fig. 3 of Hannun et al.). Their analysis therefore supports the widely held belief that nearly all cancers of all types are preventable.

In contrast, we concluded that some cancers are largely the result of environmental factors — such as those associated with exposure to cigarette smoke or sunlight, or obesity — while other cancer types are largely unavoidable. Moreover, we concluded that all cancers, of all types, are likely to be caused by a mixture of the mutations induced by external influences — avoidable in principle — and those caused by the replication of normal stem cells — unavoidable and just bad luck. Our conclusions were based on our discovery of the extraordinarily tight relationship between stem cell divisions in normal tissue and the incidence of cancer in that tissue. The striking contrast between our conclusions and those of Hannun et al. has important implications about the information that should be provided to cancer patients and the public.

We were surprised that Hannun et al. attempted to determine the proportion of individual cancers due to extrinsic factors from our stem cell data, because that is impossible to do in a reliable and mathematically sound fashion. This explains why some of the authors’ estimates of the contributions of extrinsic factors to cancer are incongruent with the voluminous epidemiologic research on these cancers. For example, Hannun et al. concluded that more than 99 percent of prostate cancers, more than 98 percent of thyroid cancers, more than 95 percent of brain cancers and more than 94 percent of testicular cancers are caused by environment factors (Fig. 3 of Hannun et al.), while epidemiologists have concluded that zero or less than 1 percent of any of these cancer types can be ascribed to extrinsic factors (http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type).

In contrast, we believe that the estimates made by decades of painstaking work by epidemiologists are accurate, i.e., that between 21 to 42 percent of cancers in the U.S. are preventable. We attempted to identify the risk factors that might have contributed to the remaining cancers. We discovered strong evidence supporting the idea that replicative mutations, made during normal stem cell divisions, are a major risk factor. Our analyses further indicated that certain cancers, such as those of the lung and skin, had a much larger non-replicative component than other cancers, such as those of the brain, bone or pancreas.

Our study was the first to provide scientific evidence to support the idea that we can now confidently tell most parents of children with cancers, as well as adult patients with certain types of cancer, that there was nothing they could have done to avoid their plight. By perpetuating the myth that virtually all cancers are due to extrinsic factors, we can inadvertently add guilt to already tragic situations. At the same time, our study confirmed the well-known importance of avoiding the known risk factors for cancer, such as cigarette smoke, sunlight and obesity.

Cristian Tomasetti
Bert Vogelstein

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In today’s news, former President Jimmy Carter, who has metastatic melanoma, revealed that he has responded well to treatment. We asked melanoma expert Evan J. Lipson, M.D., for his thoughts:

“I was pleased to hear President Carter’s report that his most recent MRI brain scan did not reveal any signs of the original cancer spots nor any new ones. While we don’t know whether President Carter is completely free of melanoma, it’s encouraging to see a 91-year-old man tolerating his treatments well and continuing to work at his foundation.

“My understanding is that the president has been treated with surgery, radiation therapy and a drug called pembrolizumab (anti-PD-1). Pembrolizumab is a relatively new medication that activates the body’s immune system to fight melanoma. In some patients, when the immune system is activated using pembrolizumab or another similar medication, nivolumab, it can attack the cancer and bring about a remission that can last for months or sometimes years. These medications have also demonstrated efficacy in some tumor types other than melanoma.

“I hope that positive outcomes like this one will be encouraging for other patients battling cancer.”

More information about melanoma and immunotherapy is available from the Johns Hopkins Melanoma Program. Look for the next issue of Promise & Progress, which will feature immunotherapy

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“We are at a crossroads, a time of discovery that’s transforming the ways we manage lung cancer,” says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus. “Lung cancer is simply not the same disease we had 10 years ago, in terms of the tools that we have available to help patients. “

Hales notes that, “Here at Johns Hopkins, we have over 25 clinical trials that evaluate innovative therapies in patients with lung cancer.  These therapies, if found to be effective, will become future therapies that benefit patients around the world.  But beyond these 25 clinical trials, we have hundreds of pre-clinical projects underway, by basic scientists, clinicians, and others, that are discovering new pathways to improve future therapies.”

All of those new research projects and findings mean that “hope is on the rise that new therapies will be available and with innovation, we can continue to improve outcomes in patients with lung cancer,” Hales says.  If you are a patient, or would like more information on management or treatments of lung cancer, call 410-955-LUNG.  To find clinical trials in which you might participate, use our search engine for cancer clinical trials and read the frequently asked questions about cancer clinical trials at the Johns Hopkins Kimmel Cancer Center.

Find out more from Dr. Hales about lung cancer, treatments for it, and innovative new research to help lung cancer patients in the free webinar, Lung Cancer: Serious Treatment for a Serious Cancer.

 

 

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Chemotherapy is a systemic therapy, and “in the past, lung cancer treatment was really a one-size-fits-all care,” says Russell K. Hales, M.D.  “Thanks to advances in treatment, we’ve been able to transition to more personalized care.  We can assess the tumor for changes that can be targeted with customized therapy, also known as molecular profiling.  These subtle changes in individual patients can then be targeted, and these targeted therapies can sometimes be very effective.”

Hales, who is a radiation oncologist at the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus, shares an example of a mutation called EML for ALK, found in just one in 20 non-small-cell lung cancers, or 5 percent of patients.  The mutation leads to the tumor cell constantly making a protein that helps it to survive.  Knowing that this happens in 5% of patients, researchers several years ago developed a drug that uniquely targeted ALK, called Crizotinib and taken in pill form. The research, published in New England Journal of Medicine, showed a reduction in tumor size and other dramatic improvements in nearly every patient, he says.

“These target therapies are helping us to better identify unique therapies to personalize care for each patient,” Hales says. Find out more from Dr. Hales about lung cancer, treatments for it, and innovative new research to help lung cancer patients in the free webinar, Lung Cancer: Serious Treatment for a Serious Cancer.

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This blog post was written by intern Amanda Garrison, a student at Florida State University. In this series, we aim to help readers understand certain scientific concepts about cancer. The concepts are topics from the Johns Hopkins Kimmel Cancer Center’s annual lecture series Fundamentals of Cancer, Cause to Cure which is directed by oncologist Leisha Emens, M.D., Ph.D. and available to researchers and staff working in the cancer center.

Most people have heard of and have a basic understanding of genetics, but have you ever heard of epigenetics? If not, then you’re in the same spot I was a few days ago.

By definition, the term epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence; a change in phenotype without a change in genotype. It’s a regular and natural occurrence but can be influenced by several factors, such as age, lifestyle, and disease state. Epigenetic modifications can display as commonly as the manner in which cells differentiate to end up as skin cells, liver cells, brain cells, etc. Or, epigenetic change can have more damaging edicts that can result in diseases, such as cancer.

So, how does this scientific process apply to cancer treatments, and what are scientists finding out about it? Here’s some of the latest research underway at the Johns Hopkins Kimmel Cancer Center.

Drs. Stephen Baylin, Cynthia Zahnow, and Drew Pardoll studied patients with advanced lung, breast, and colon cancers in which an immune system-related gene called PDL1 was activated. Laboratory studies indicated that its expression in lung cancer cells may be enhanced by therapies that target epigenetic processes. Dr. Pardoll believes that using a drug to block PD-L1 or a similar gene called PD-1 in unison with epigenetic therapy could change the balance of immune effects of the treatment.

Scientists have also found that cancer cells play a bit of hide-and-seek with the immune system. But new research is revealing how to find cancer’s hiding spots.

Cancer has an immune evasion signal and, in order to survive, cancer cells need to partially adapt to their environment. When treated with epigenetic drugs, the ability to evade the immune system is broken and cancer cells are tricked into sending out signals for the immune cells to identify and destroy them. But they also express PD-L1 proteins to shield against immune attack. After going back to the lab with this knowledge, Drs. Baylin, Zahnow, Nita Abuja, and John Wrangle found that many genes get reactivated, but about 20 percent of them are related to immune regulation, which is a much bigger component than they thought, according to Dr. Ahuja.

They found a small subset of the genes they identified constitute a viral defense pathway that are epigenetically programmed to avoid detection by the immune system. By using a drug to reverse this programming, essentially performing a form of “viral mimicry,” scientists may be able to force the cancer cells out of hiding and make them more vulnerable to treatment, or better yet, allow the immune system to kill the cancer altogether.

Read more about epigenetics.

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