Alex's Lemonade Stand Foundation for Childhood Cancer

Osteosarcoma is a tumor of the bone that typically occurs in adolescents and young adults. Many patients with osteosarcoma are cured of their disease, but a significant proportion of patients are not. The primary approach to treating osteosarcoma includes surgery and chemotherapy. Unfortunately, this approach has not improved for several decades. One of the reasons why it has been difficult to develop new treatment approaches for osteosarcoma patients is that we don’t fully understand how these tumors develop.

Survival of children with AML remains poor because our treatments haven't changed much in 30 years. AML is a disease of DNA – mutations found in leukemia DNA are not seen in normal blood cells. However, we think that the physical structure of DNA itself could also be important in leukemia development. If the DNA in a cell was stretched out, it would be six feet long, yet it has to be tightly packed to fit inside the head of a pin. When we looked at leukemia under the microscope, the DNA was not as tightly wound as it should be.

When pediatric leukemias recur, they are often harder to treat because they have developed resistance to the broad spectrum of standard treatments, such as chemotherapy, radiation, and modern cellular and immunotherapies. Most pediatric leukemia treatments target either the cancer cell’s DNA or protein, but often cannot distinguish between leukemia cells and normal cells, leading to unwanted side effects and toxicities. For our proposed Innovator project, we will focus on a distinct target of the leukemia cell – its membrane coating or “plasma membrane”.

Cancer is the leading cause of disease-related death among American children. Despite significant progress in recent decades, which has provided the possibility of a cure for many diagnosed children, we have not succeeded in improving the prognosis for certain cancer subtypes that have seen no advancement in the last 50 years. A key player in many of these aggressive subtypes is a gene called MYC. When MYC becomes overactive, it can cause cells to grow and divide uncontrollably, as well as evade the body's natural anti-cancer mechanisms.