Surgical removal of a tissue sample is now the standard for diagnosing cancer. Such procedures, known as biopsies, are accurate but only offer a snapshot of the tumor at a single moment in time.

Monitoring a tumor for weeks or months after the biopsy, tracking its growth and how it responds to treatment, would be much more valuable, says Michael Cima, MIT professor of materials science and engineering, who has developed the first implantable device that can do just that.

Cima and his colleagues recently reported that their device successfully tracked a tumor marker in mice for one month. The work is described in a paper published online in the journal Biosensors & Bioelectronics in April.

Such implants could one day provide up-to-the-minute information about what a tumor is doing — whether it is growing or shrinking, how it’s responding to treatment, and whether it has metastasized or is about to do so.

“What this does is basically take the lab and put it in the patient,” said Cima, who is also an investigator at the David H. Koch Institute for Integrative Cancer Research at MIT.

The devices, which could be implanted at the time of biopsy, could also be tailored to monitor chemotherapy agents, allowing doctors to determine whether cancer drugs are reaching the tumors. They can also be designed to measure pH (acidity) or oxygen levels, which reveal tumor metabolism and how it is responding to therapy.

With current tools for detecting whether a tumor has spread, such as biopsy, by the time you have test results it’s too late to prevent metastasis, said Cima.

“This is one of the tools we’re going to need if we’re going to turn cancer from a death sentence to a manageable disease,” he said.

In the Biosensors & Bioelectronics study, human tumors were transplanted into the mice, and the researchers then used the implants to track levels of human chorionic gonadotropin, a hormone produced by human tumor cells.

The cylindrical, 5-millimeter implant contains magnetic nanoparticles coated with antibodies specific to the target molecules. Target molecules enter the implant through a semipermeable membrane, bind to the particles and cause them to clump together. That clumping can be detected by MRI (magnetic resonance imaging).

The device is made of a polymer called polyethylene, which is commonly used in orthopedic implants. The semipermeable membrane, which allows target molecules to enter but keeps the magnetic nanoparticles trapped inside, is made of polycarbonate, a compound used in many plastics.

Cima said he believes an implant to test for pH levels could be commercially available in a few years, followed by devices to test for complex chemicals such as hormones and drugs.

Lead author of the paper is Karen Daniel, a recent MIT PhD recipient. Other authors are recent PhD recipients Grace Kim and Christophoros Vassiliou; Marilyn Galindo, research affiliate in the Harvard-MIT Division of Health Sciences and Technology; Alexander Guimares, a radiologist at Massachusetts General Hospital; Ralph Weissleder, a professor of radiology at Harvard Medical School; Al Charest, visiting assistant professor of biology at MIT; and Institute Professor Robert Langer.

The research was funded by the National Cancer Institute Centers of Cancer Nanotechnology Excellence and the National Science Foundation.

Source:
Elizabeth Thomson

Massachusetts Institute of Technology

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“Crunching data from published studies, the authors found that treating a lung-cancer patient with Wall Street Journal reports. The study, which estimates that the life of each American who dies or cancer could be extended by one year at the cost of $440 billion, was published in the Journal of the National Cancer Institute.

The high cost and relatively low benefit points to “one of the thorniest questions facing lawmakers working on the overhaul of the U.S. health-care system”: reducing growing health care spending in the last months of patient’s lives. “Some countries, like the United Kingdom, agree to pay for expensive drugs only if they meet a certain threshold of efficacy, but no such rationing exists in the U.S.,” the Journal reports.

“While some policy experts consider the rationing of health-care resources inevitable in the quest to control medical spending, many Americans have long resisted putting the collective fiscal good over their individual health” (Johnson, 6/29).

This information was reprinted from kaiserhealthnews.org with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives and sign up for email delivery at kaiserhealthnews.org.

© Henry J. Kaiser Family Foundation. All rights reserved.

View drug information on Erbitux.

The decision to use expensive cancer therapies that typically produce only a relatively short extension of survival is a serious ethical dilemma in the U.S. that needs to be addressed by the oncology community, according to a commentary published online June 29 in the Journal of the National Cancer Institute.

Tito Fojo, M.D., Ph.D., of the Medical Oncology Branch, Center of Cancer Research at the National Cancer Institute, in Bethesda, Md., and Christine Grady, Ph.D., of the Department of Bioethics, the Clinical Center at the National Institutes of Health, tackle the controversy concerning the life-extending benefits of certain cancer drugs and the extent to which their cost should factor in deliberations.

The authors illustrate cost-benefit relationships for several cancer drugs, including cetuximab for treatment of non-small cell lung cancer, touted as “practice changing” and new standards of care by professional societies, including the American Society of Clinical Oncology.

They ask, “Is an additional 1.7 months [the additional overall survival for colorectal cancer patients treated with cetuximab] a benefit regardless of costs and side effects?”

According to Fojo and Grady, in the U.S., 18 weeks of cetuximab treatment for non-small cell lung cancer, which was found to extend life by 1.2 months, costs an average of $80,000, which translates into an expenditure of $800,000 to prolong the life of one patient by 1 year. At this rate, it would cost $440 billion annually, an amount 100 times NCI’s budget, to extend the lives of 550,000 Americans who die of cancer annually by 1 year.

To address the issue, the commentators recommend that studies powered to detect a survival advantage of two months or less should test only interventions that can be marketed at a cost of less than $20,000 for a course of treatment.

Every life is of infinite value, the authors say, but spiraling costs of cancer care makes this dilemma inescapable.

“The current situation cannot continue. We cannot ignore the cumulative costs of the tests and treatments we recommend and prescribe. As the agents of change, professional societies, including their academic and practicing oncologist members, must lead the way,” the authors write. “The time to start is now.”

Citation: Fojo T. and Grady C. How Much Is Life Worth: Cetuximab, Non - Small Cell Lung Cancer, and the $440 Billion Question J Natl Cancer Inst 2009, 101: 1-5.

Source:
Steve Graff

Journal of the National Cancer Institute

The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting exceptional early career researchers and innovative cancer research, named 17 new Damon Runyon Fellows at its May 2009 Fellowship Award Committee review. The recipients of this prestigious, three-year award are outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators across the country. The Fellowship is specifically intended to encourage the nation’s most promising young scientists to pursue careers in cancer research by providing them with independent funding ($140,000 each) to work on innovative projects.

Of the 17 new Fellows, six will be named HHMI Fellows in recognition of support from the Howard Hughes Medical Institute (HHMI), which will fund $1M in Damon Runyon Fellowships each year.

May 2009 Damon Runyon Fellows:

Orkun Akin, PhD [HHMI Fellow] with his sponsor S. Lawrence Zipursky, PhD, at the University of California, Los Angeles, California, is studying cell motility in the context of the developing nervous system. He aims to understand how external cues are coupled to changes in the actin cytoskeleton. As cell motility is essential for normal development as well as for cancer metastasis, new insights into the basic biology of motility carry the promise of new therapies and approaches to cancer treatment.

Yimon Aye, PhD, with her sponsor JoAnne Stubbe, PhD, at the Massachusetts Institute of Technology, Cambridge, Massachusetts, is studying the mechanism and regulation of ribonucleotide reductases (RNRs), enzymes that play an essential role in making deoxynucleotides (the “building blocks” of DNA). RNRs are overexpressed in cancer cells, making them an ideal target for cancer drugs. Her work will focus on understanding the mechanism of a new drug called Triapine, which may prevent the replication of tumor cells and is currently being tested in Phase II and III clinical trials.

Sean C. Bendall, PhD, with his sponsor Garry P. Nolan, PhD, at Stanford University, Stanford, California, is using breakthrough single-cell analysis techniques to investigate how normal regulatory cell signaling networks are rewired, allowing cancer to grow unchecked. By understanding these events, he aims to contribute to the development of more effective diagnostics and treatments to improve clinical outcomes.

Robert K. Bradley, PhD, with his sponsor Christopher B. Burge, PhD, at the Massachusetts Institute of Technology, Cambridge, Massachusetts, is studying the proteins that regulate splicing, a process by which a single gene may be expressed as multiple, distinct protein forms. Gaining a better understanding of this process is important, as disruption of normal splicing can give rise to cancer.

Matthew F. Calabrese, PhD [HHMI Fellow] with his sponsor Brenda A. Schulman, PhD, at St. Jude Children’s Research Hospital, Memphis, Tennessee, is studying how cell division is regulated, in part, by the attachment of a protein called ubiquitin to other proteins throughout the cell. Understanding how ubiqutin is attached to its targets and how this attachment is recognized by cellular machinery is critical to understanding normal cell division as well as unregulated cell division associated with cancer.

Jianfu Chen, PhD [HHMI Fellow] with his sponsor Lee A. Niswander, PhD, at the University of Colorado Denver, Colorado, is studying molecular mechanisms of gene-folic acid (FA) interactions. The goals of his research are to understand how FA interacts with our genome and to determine whether it has a role in cancer prevention.

Won-Suk Chung, PhD, with his sponsor Ben A. Barres, MD, PhD, at Stanford University, Stanford, California, is investigating the development and function of brain cells called astrocytes. Astrocytes have been shown only recently to play critical roles in neuronal development and diseases, such as brain tumors (astrocytomas). Understanding how astrocytes are generated and maintained in the brain will help to develop better strategies for treating astrocytomas.

Nadya Dimitrova, PhD, with her sponsor Tyler Jacks, PhD, at the Massachusetts Institute of Technology, Cambridge, Massachusetts, is studying the role of a novel class of RNA molecules, lincRNAs, in tumor suppression. By dissecting the mechanism by which lincRNAs influence tumor suppressor pathways, she hopes to identify new markers for cancer diagnosis as well as novel approaches for effective cancer treatment.

Chuan-Hsiang Huang, MD, PhD [Harold L. Plotnick Fellow] with his sponsor Peter N. Devreotes, PhD, at The Johns Hopkins University, Baltimore, Maryland, is studying chemotaxis, a process by which cells migrate in response to naturally-occurring chemical cues in the human body. This process is essential for normal cellular movements as well as for the spread of cancer cells (metastasis). Better understanding of chemotaxis will facilitate the development of strategies to block cancer metastasis.

Daniel H. Kim, PhD, with his sponsor Jeannie T. Lee, MD, PhD, at Massachusetts General Hospital, Boston, Massachusetts, is studying how noncoding RNAs (unique RNAs that do not make proteins) control gene expression during a developmental process in females called X-inactivation, which turns off all genes on an entire chromosome. His work may provide insights into novel regulatory roles for noncoding RNAs in silencing tumor suppressor genes, while potentially revealing new therapeutic targets for the treatment of many types of cancer.

Liana F. Lareau, PhD [HHMI Fellow] with her sponsor Patrick O. Brown, MD, PhD, at Stanford University, Stanford, California, is investigating how the cell regulates translation, the process that turns the information in our genes into proteins. Misregulation of protein production is a hallmark of many forms of cancer.

Josselin Milloz, PhD, with his sponsor Sharad Ramanathan, PhD, at Harvard University, Cambridge, Massachusetts, aims to understand how autophagy, the process of cellular “self-cannibalism,” is involved in a large number of cancers. Learning how autophagy is coordinated with other cellular processes will better elucidate its multiple roles in cancer.

Taiowa A. Montgomery, PhD, with his sponsor Gary Ruvkun, PhD, at Massachusetts General Hospital, Boston, Massachusetts, is studying mechanisms of gene silencing by a class of small regulatory molecules called microRNAs. In addition to having essential roles in development, microRNAs can act as oncogenes or as tumor suppressors. MicroRNAs have tremendous potential to be used therapeutically to prevent and treat cancer.

Benjamin R. Myers, PhD, with his sponsor Philip A. Beachy, PhD, at Stanford University, Stanford, California, is studying the function of the Hedgehog signaling pathway, in particular, how inappropriate activation of this pathway can lead to the initiation and growth of tumors. Insights into Hedgehog signaling may allow for the development of more potent and specific forms of cancer therapy.

Jared T. Nordman, PhD [HHMI Fellow] with his sponsor Terry L. Orr-Weaver, PhD, at the Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, is working to identify genes that are necessary to ensure accurate and efficient duplication of the genome. Identifying genes involved in the regulation of DNA replication is critical for understanding how a normal cell can become a tumor cell.

Sharsti L. Sandall, PhD, with her sponsor D. Leanne Jones, PhD, at the Salk Institute for Biological Studies, La Jolla, California, is investigating the mechanisms governing stem cell fate within the native environment or “niche.” These studies may reveal paradigms of how a normal stem cell niche can be converted to an environment that supports cancer self-renewal; this could ultimately provide strategies to target the environment as a novel anticancer therapy.

Ilan Wapinski, PhD [HHMI Fellow] with his sponsor Roy Kishony, PhD, at Harvard Medical School, Boston, Massachusetts, is studying how changes in gene regulation impact cellular growth rates. Understanding these processes will help to understand how cancer cells can outgrow healthy ones in the human body.

Source:
Yung S. Lie, Ph.D.
Damon Runyon Cancer Research Foundation