Zachary Morris has certainly done some memorable things. As a Rhodes Scholar, he once attended an evening reception at Buckingham Palace, played a game of pick-up football with former President Bill Clinton, and traveled to South Africa to take a Robben Island Prison tour, led by the late Nelson Mandela. But something the young radiation oncologist did during his medical residency could prove even more momentous. He received a special opportunity from the American Board of Radiology to join others in studying how to pair radiation therapy with the emerging cancer treatment strategy of immunotherapy.
Morris’s studies in animals showed that the two treatments have a unique synergy, generating a sustained tumor-specific immune response that’s more potent than either therapy alone. But getting this combination therapy just right to optimize its cancer-fighting abilities remains complicated. Morris, now a researcher and clinician at the University of Wisconsin School of Medicine and Public Health, Madison, has received a 2017 NIH Director’s Early Independence Award to look deeper into this promising approach. He and his collaborators will use what they learn to better inform their future early stage clinical trials of radio-immunotherapy starting with melanoma, head and neck cancers, and neuroblastoma.
Tags: 2017 NIH Director’s Early Independence Award, cancer, dinutuximab, head and neck cancer, IL-2, immunotherapy, low-dose radiation, lymphoma, melanoma, neuroblastoma, oncology, radiation, radiation oncology, radiation therapy, radio-immunotherapy, Tregs
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.
Tags: Alzheimer’s disease, brain, cancer, cancer drug resistance, CRISPR/Cas9, DNA editing, drug resistance, Forbes "30 under 30", gene editing, gene therapy, gene-editing technology, genome engineering, melanoma, ncRNA, NIH Director's Early Independence Award, noncoding RNA, oncology, RNA, RNA editing tools, Salk Institute for Biological Studies, skin cancer
It’s still the case in most medical care systems that cancers are classified mainly by the type of tissue or part of the body in which they arose—lung, brain, breast, colon, pancreas, and so on. But a radical change is underway. Thanks to advances in scientific knowledge and DNA sequencing technology, researchers are identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that arise in totally different parts of the body can sometimes have a lot in common. Not only can molecular analysis refine diagnosis and provide new insights into what’s driving the growth of a specific tumor, it may also point to the treatment strategy with the greatest chance of helping a particular patient.
The latest cancer to undergo such rigorous, comprehensive molecular analysis is malignant melanoma. While melanoma can rarely arise in the eye and a few other parts of the body, this report focused on the more familiar “cutaneous melanoma,” a deadly and increasingly common form of skin cancer . Reporting in the journal Cell , The Cancer Genome Atlas (TCGA) Network says it has identified four distinct molecular subtypes of melanoma. In addition, the NIH-funded network identified an immune signature that spans all four subtypes. Together, these achievements establish a much-needed framework that may guide decisions about which targeted drug, immunotherapy, or combination of therapies to try in an individual with melanoma.
Tags: BRAF, cancer, cancer subtypes, cutaneous melanoma, genomics, immune signature, immunotherapy, LCK, malignant melanoma, melanoma, melanoma biomarker, melanoma subtypes, melanoma therapy, molecular analysis, molecular fingerprint, NF1, precision medicine, Precision Medicine Initiative, precision oncology, RAS, skin cancer, TCGA, The Cancer Genome Atlas, UV radiation
It would be great if we could knock out cancer with a single punch. But the more we learn about cancer’s molecular complexities and the immune system’s response to tumors, the more it appears that we may need a precise combination of blows to defeat a patient’s cancer permanently, with no need for a later rematch. One cancer that provides us with a ringside seat on the powerful potential—and tough challenges—of targeted combination therapy is melanoma, especially the approximately 50% of advanced tumors with a specific “driver” mutation in the BRAF gene .
Drugs that target cells carrying BRAF mutations initially provided great hope for melanoma, with many reports of dramatic shrinkage of tumors in patients with advanced disease. But almost invariably, the disease recurred and was no longer responsive to those same drugs. A few years ago, researchers thought they’d come up with a solid combination to fight BRAF-mutant melanoma: a one-two punch that paired a BRAF-inhibiting drug with an agent that sensitized the immune system . However, when that combo was tested in humans, the clinical trial had to be stopped early because of serious liver toxicity . Now, in a mouse study published in Science Translational Medicine, NIH-funded researchers at the University of California, Los Angeles (UCLA) provide renewed hope for a safe, effective combination therapy for melanoma—with a strategy that adds a third drug to the mix .
It may surprise you to learn that the poised young woman featured in this video was a sophomore in high school at the time the film was made. Today, Emily Ashkin is a high school senior with impressive laboratory experience and science awards to her name. As it happens, she’s also introducing me when I deliver a keynote address at the Melanoma Research Alliance’s annual scientific meeting — today, here in Washington, D.C.
What struck me most when I heard Emily’s story was her fearlessness. When mentoring young students, helping some to believe in themselves can be a real challenge. Not Emily. She faces her challenges by seeking solutions, asking—as she does in the video—“Why can’t that be me?”