Stories about: bone tumor

Cancer researchers hit a bullseye with a new drug target for Ewing sarcoma

Cell staining shows the lethal efficacy of CDK+PARP inhibitors against Ewing sarcoma
Fluorescent staining shows how PARP and CDK12 inhibitors combine to deal a lethal blow to Ewing sarcoma. In the top row, green represents locations of DNA damage incurred by Ewing sarcoma cells. In the bottom row, red represents DNA repair activity. Together, PARP and CDK12 inhibitors lead to Ewing sarcoma cell death.

Screening a class of recently-developed drug compounds — so-called “CDK inhibitors” capable of blocking CDK7/12/13 proteins — against hundreds of different human cancer cell lines, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have found that CDK12 inhibitors pack a particularly lethal punch to Ewing sarcoma, a rare cancer typically affecting children and young adults.

“No one has previously considered CDK12 inhibition as a way to combat Ewing sarcoma,” says Kimberly Stegmaier, MD, senior author of the new Cancer Cell paper that describes the findings.

In 2014, Nathaneal Gray, PhD, co-author on the new paper, and his team were the first to develop CDK inhibitors.

Some individuals were entirely cured of the disease

“Now, in mice, we’ve shown that Ewing sarcoma cells die if CDK12 is knocked out genetically or chemically inhibited,” Stegmaier says. What’s more, her team has discovered that CDK12 inhibition can be combined with another drug, called a PARP inhibitor, to double down on Ewing sarcoma cells.

The revelation that CDK12 inhibition can kill Ewing sarcoma cells brings a surge of hope to the field of pediatric oncology, which has long been challenged to find new drugs against childhood cancers.

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Mining similarities in pediatric and canine bone cancer to help both children and pets

dogs aid fight against osteosarcoma

In March 2016, Ollie, a therapy dog at Boston Children’s Hospital, paid a bedside visit to 7-year-old Carter Mock. The pug and the boy had something in common: Both had lost limbs to the bone cancer osteosarcoma. Ollie’s left front leg had been amputated at the shoulder, while Carter had just had a new knee fashioned from his ankle in a procedure called rotationplasty.

Biologically, the osteosarcoma that dogs develop is remarkably similar to osteosarcoma in children and youths. The tumors develop primarily in the long bones, and the spread of tumor cells to the lungs represents the most significant threat and challenge. Similar chemotherapy agents are used in both dogs and human patients to kill residual cancer cells. Researchers are now mining these similarities in a quest for new treatments to benefit pets and people alike.

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Is one look better than two? Assessing bone tumor removal during surgery

Wordle graphic of words associated with bone tumor surgery and intraoperative assessment.
One assessment of tumor margins during bone tumor removal surgery may suffice where two are done now.
Improvements in imaging technologies have made the process of defining the extent of bone tumors like osteosarcomas increasingly accurate.

But while it’s easier than ever to say, “The tumor starts here and ends here,” when removing a bone tumor surgically, surgeons still need to take a moment during the operation to check the edges (or “margins”) of the removed and remaining bone for any signs of remaining tumor, a step called intraoperative assessment.

“You need to make sure the tumor has been completely removed and a safe amount of normal tissue remains as a buffer,” says Sara Vargas, MD, director of patient safety and quality in Boston Children’s Hospital’s Department of Pathology. “Achieving a margin that is free of tumor reduces a patient’s long-term risk of local tumor recurrence.”

During surgery, there are two ways to do the assessment, each method providing a check on the other: gross split specimen inspection and frozen section inspection.

The two methods, which are often done either simultaneously or in tandem during surgery, are quite different.

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