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oncology

Study Shows DNA Sequencing Brings Greater Precision to Childhood Cancer

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Dr. Plon with a patient and her family

Caption: Baylor’s Sharon Plon consults with a family at the Texas Children’s Cancer Center in Houston.
Credit: Paul V. Kuntz/Texas Children’s Hospital

An impressive number of fundamental advances in our understanding of cancer have occurred over the past several decades. One of the most profound is the realization that cancer is a disease of the genome, driven by a wide array of changes in DNA—some in the germline and affecting all cells of the body, but most occurring in individual cells during life (so-called “somatic mutations”). As the technology for sequencing cancer genomes has advanced, we are learning that virtually all cancers carry a unique set of mutations. Most are DNA copying errors of no significance (we call those “passengers”), but a few of them occur in genes that regulate cell growth and contribute causatively to the cancer (we call those “drivers”). We are now learning that it may be far more important for treating cancer to figure out what driver mutations are present in a patient’s tumor than to identify in which organ it arose. And, as a new study shows, this approach even appears to have potential to help cancer’s littlest victims.

Using genomic technology to analyze both tumor and blood samples from a large number of children who’d been newly diagnosed with cancer, an NIH-funded research team uncovered genetic clues with the potential to refine diagnosis, identify inherited cancer susceptibility, or guide treatment for nearly 40 percent of the children [1]. The potential driver mutations spanned a broad spectrum of genes previously implicated not only in pediatric cancers, but also in adult cancers. While much more work remains to determine how genomic analyses can be used to devise precise, new strategies for treating kids with cancer, the study provides an excellent example of the kind of research that NIH hopes to accelerate under the nation’s new cancer “moonshot,”  a research initiative recently announced by the President and being led by the Vice President.


Cool Videos: Spying on Cancer Cell Invasion

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Spying on Cancer Cell Invation

If you’re a fan of the Mission: Impossible spy thrillers, you might think that secret agent Ethan Hunt has done it all. But here’s a potentially life-saving mission that his force has yet to undertake: spying on cancer cells. Never fear—some scientific sleuths already have!

So, have a look at this bio-action flick recently featured in the American Society for Cell Biology’s 2015 Celldance video series. Without giving too much of the plot away, let me just say that it involves cancer cells escaping from a breast tumor and spreading, or metastasizing, to other parts of the body. Along the way, those dastardly cancer cells take advantage of collagen fibers to make a tight-rope getaway and recruit key immune cells, called macrophages, to serve as double agents to aid and abet their diabolical spread.


Snapshots of Life: Bring on the Confetti!

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Renal Pericytes

Credit: Heinz Baumann, Sean T. Glenn, Mary Kay Ellsworth, and Kenneth W. Gross, Roswell Park Cancer Institute, Buffalo, NY

If this explosion of color reminds you of confetti, you’re not alone—scientists think it does too. In fact, they’ve even given the name “Confetti mouse” to a strain of mice genetically engineered so that their cells glow in various combinations of red, blue, yellow, or green markers, depending on what particular proteins those cells are producing. This color coding, demonstrated here in mouse kidney cells, can be especially useful in cancer research, shedding light on subtle molecular differences among tumors and providing clues to what may be driving the spread, or metastasis, of cancer cells beyond the original tumor site.

Not only is the Confetti mouse a valuable scientific tool, this image recently earned Heinz Baumann and colleagues at the Roswell Park Cancer Institute, Buffalo, NY, a place of honor in the Federation of American Societies for Experimental Biology’s 2015 Bioart competition. Working in the NIH-funded lab of Kenneth Gross, Baumann’s team created a Confetti mouse system that enables them to manipulate and explore in exquisite detail the expression of proteins in renal pericytes, a type of cell associated with the blood filtration system in the kidney.


Creative Minds: Applying CRISPR Technology to Cancer Drug Resistance

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Patrick Hsu

Patrick Hsu

As a child, Patrick Hsu once settled a disagreement with his mother over antibacterial wipes by testing them in controlled experiments in the kitchen. When the family moved to Palo Alto, CA, instead of trying out for the football team or asking to borrow the family car like other high school kids might have done, Hsu went knocking on doors of scientists at Stanford University. He found his way into a neuroscience lab, where he gained experience with the fundamental tools of biology and a fascination for understanding how the brain works. But Hsu would soon become impatient with the tools that were available to ask some of the big questions he wanted to study.

As a Salk Helmsley Fellow and principal investigator at the Salk Institute for Biological Studies, La Jolla, CA, Hsu now works at the intersection of bioengineering, genomics, and neuroscience with a DNA editing tool called CRISPR/Cas9 that is revolutionizing the way scientists can ask and answer those big questions. (This blog has previously featured several examples of how this technology is revolutionizing biomedical research.) Hsu has received a 2015 NIH Director’s Early Independence award to adapt CRISPR/Cas9 technology so its use can be extended to that other critically important information-containing nucleic acid—RNA.Specifically, Hsu aims to develop ways to use this new tool to examine the role of a certain type of RNA in cancer drug resistance.


Cancer Metastasis: Trying to Catch the Culprits Earlier

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Scaffold

Caption: Scaffold of a cancer cell-attracting implant as seen by scanning electron microscopy.
Credit: Laboratory of Lonnie Shea

For many people diagnosed with cancer localized to the breast, prostate, or another organ, the outlook after treatment is really quite good. Still, most require follow-up testing because there remains a risk of the cancer recurring, particularly in the first five years after a tumor is removed. Catching recurrence at an early, treatable stage can be difficult because even a small number of new or “leftover” tumor cells have the ability to enter the bloodstream or lymphatics and silently spread from the original tumor site and into the lung, brain, liver, and other vital organs—the dangerous process of metastasis. What if there was a way to sound the alarm much earlier—to detect tumor cells just as they are starting to spread?

Reporting in Nature Communications [1], an NIH-funded research team from the University of Michigan, Ann Arbor, and Northwestern University, Evanston, IL, has developed an experimental device that appears to fit the bill. When these tiny, biodegradable scaffolds were implanted in mice with a highly metastatic form of breast cancer, the devices attracted and captured migrating cancer cells, making rapid detection possible via a special imaging system. If the results are reproduced in additional tests in animals and humans, such devices might enable earlier identification—and thereby treatment—of one of the biggest challenges in oncology today: metastatic cancer.


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