Three children Alejandro Gutierrez, MD, treated for leukemia during his fellowship at Boston Children’s Hospital still haunt him more than a decade later. One 15-year-old boy died from the toxicity of the drugs he was given; the other two patients went through the whole treatment only to die when their leukemia came back. “That really prompted a deep frustration with the status quo,” Gutierrez recalls. “It’s motivated everything I’ve done in the lab since then.”
Gutierrez, now a researcher in the Division of Hematology/Oncology, has made it his mission to figure out why leukemia treatments cure some patients but not others. And in today’s issue of Cancer Cell, he and 15 colleagues report progress on two important fronts: They shed light on how leukemia cells become resistant to drugs, and they describe how two drugs used in combination may overcome that resistance, offering new hope to thousands of children and adults with leukemia.
Most of the time, cancer cells do a combination of two things: they overexpress genes that drive tumor growth and they lose normal genes that typically suppress tumors. No two tumors are exactly alike, but some combination of these two effects is usually what results in cancer. Now, for the first time, researchers have shown that it’s possible to treat cancer by delivering a gene that naturally suppresses tumors.
Researchers from Boston Children’s Hospital, Brigham and Women’s Hospital and Memorial Sloan Kettering Cancer Center combined their cancer biology and nanomaterials expertise and developed a therapeutic capable of delivering a tumor suppressor gene known as PTEN, the loss of which can allow tumors to grow unchecked.
In several preclinical models, their PTEN–boosting therapeutic was able to inhibit tumor growth. Their findings were published yesterday in Nature Biomedical Engineering. …
Cancer and other diseases are now understood to spring from a complex interplay of biological factors rather than any one isolated origin. New research reveals that an equally-nuanced approach to treating high-risk neuroblastoma may be the most effective way to curb tumor growth.
One challenge in treating pediatric cancers like neuroblastoma is that they are not initiated from the same kinds of genetic mutations as adult cancers, which usually arise from mutations related to an accumulation of DNA replication errors or environmental factors. In contrast, childhood cancers more often stem from genetic duplications, deletions or translocations, the latter of which occurs when a gene sequence switches its location from one chromosome to another. …
As we’ve seen this week on Vector, some rare childhood cancers such as medulloblastoma and neuroblastoma are starting to give up their molecular secrets, raising the possibility (and in medulloblastoma’s case, the reality) of precision treatments. Many cancers, though, are so rare that there aren’t even cell lines in which to study them. Yet they could hold important insights. The first tumor suppressor gene, Rb, was discovered in retinoblastoma, a cancer affecting a mere 500 U.S. children each year.
The findings also have implications for other solid tumors in which let-7 is lost, such as Wilms tumor, lung, breast, ovarian and cervical cancers, says first author John Powers, PhD, of the Division of Pediatric Hematology/Oncology at Boston Children’s Hospital. …
For almost a century, brain tumors have been diagnosed based on their appearance under a microscope and classified by their resemblance to the brain cells from which they are derived. For example, astrocytoma ends with “-oma” to designate that it is a tumor derived from astrocytes. In some cases, especially in children, brain tumors resemble cells in the developing brain and are named for the cells from which they are presumed to arise, such as pineoblastoma for developing cells within the pineal gland or medulloblastoma for developing cells within the cerebellum or brainstem.