BY Morten Busch
Ewing sarcoma is a life-threatening tumour growing in bones that especially affects teenagers. In contrast to many other types of cancer, only modest advances have been made in treating Ewing sarcoma in the past two decades because it resists chemotherapy. New research shows that combining several types of chemotherapy may be more effective.
The early death of children and adolescents from the disease profoundly affects their immediate families. Researchers are also concerned because, despite intensive efforts, there have been virtually no advances in treating people with Ewing sarcoma, the second-most common form of bone cancer, from which almost half die. Now an international research team with Danish participation has discovered a possible treatment breakthrough.
This dreaded disease especially affects adolescents. The challenge is that Ewing sarcoma results from major changes in how young people regulate normal tissue instead of specific genetic mutations. This makes it harder to direct chemotherapy to the diseased tissue, making it easier for the tumour to resist treatment.
The challenge with therapy using one chemical agent is that the chemotherapy only blocks one metabolic pathway, and the tumour can easily find another pathway. Treatment strategies for cancer are therefore increasingly based on combining different types of chemotherapy that block several pathways simultaneously. Unfortunately, this has previously been largely unsuccessful for Ewing sarcoma.
By systematically screening the tumour cells from three different types of Ewing sarcoma, the international research team has measured the interactions and combinations of a comprehensive array of specific chemicals. This strategy appears to have succeeded. But this systematic approach provided benefits beyond discovering how to optimally combine existing types of chemotherapy.
The researchers also identified two specific molecular targets, PKC412 and IGF-1R, which they believe are the obvious Achilles heel of the tumour cells. The researchers propose to focus the right combinations of different types of chemotherapy on these targets to treat Ewing sarcoma, and they believe that this can be easily and rapidly implemented clinically. The researchers hope that their results will help to save many young people from an early death.
“Combinatorial drug screening identifies Ewing sarcoma–specific sensitivities” has been published in Molecular Cancer Therapy. Researchers from the Novo Nordisk Foundation Center for Protein Research participated in the international research collaboration.