Research Directions for Childhood Cancer

Brent Weston, M.D., and Harrison McKinion at UNC Lineberger Comprehensive Cancer Center

Harrison McKinion (right) was diagnosed with B-cell acute lymphoblastic leukemia in which the genes EBF1 and PDGFRB were rearranged. Brent Weston, M.D., of the UNC Lineberger Comprehensive Cancer Center, reported that Harrison responded well to targeted therapy with imatinib.

Credit: Ginger McKinion

Making rapid progress against childhood cancers is a high-priority goal for NCI.

Our understanding of the biology underlying cancers that occur in children and adolescents has increased tremendously in the past decade, but there are still critical gaps in our knowledge. NCI has identified a number of areas in which more research is needed and has identified opportunities to use new approaches to gain additional insights into childhood cancers.

Promising Areas of Research

Immunotherapies for Childhood Cancers

Immunotherapies are treatments that restore or enhance the immune system’s natural ability to fight cancer. In just the past few years alone, the rapidly advancing field of cancer immunology has produced several new methods for treating cancer.

One example is chimeric antigen receptor (CAR) T-cell therapy, which has been shown to induce sustained remissions in pediatric patients with acute lymphoblastic leukemia (e.g., as seen in clinical trials of CTLO19 and CD19-CAR T). This therapeutic approach arose from decades of research on how the immune system works and how to manipulate it for clinical benefit. Early investigations by NCI scientists Lawrence Samelson and Richard Klausner on the structure of the T-cell receptor and the role this receptor plays in T cell activation, as well as the pioneering work of NCI’s Steven Rosenberg and his colleagues on an immunotherapy technique called adoptive cell transfer (ACT), helped pave the way for this major treatment advance.

The following are selected clinical trials of immunotherapy in pediatric and young adult patients that are currently underway in the NCI Center for Cancer Research’s Pediatric Oncology Branch:

  • A Phase I Trial of T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Children and Young Adults With GD2+ Solid Tumors (NCT02107963)
  • Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults with Recurrent or Refractory CD22-expressing B-Cell Malignancies (NCT02315612)

In addition, the Children’s Oncology Group (COG) and the Pediatric Brain Tumor Consortium are evaluating immunotherapy treatments for selected childhood cancers, including:

  • Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas (NCT02304458)
  • Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas or Diffuse Intrinsic Pontine Gliomas (NCT02359565)
  • Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (NCT02101853)

Molecularly Targeted Therapies

Molecularly targeted therapies are drugs or other substances that kill cancer cells by targeting specific molecules that are necessary for cancer cells to grow and survive. These therapies can be small molecule inhibitors, monoclonal antibodies, or antibody-drug conjugates.

The following are selected clinical trials of targeted therapy in pediatric and young adult patients that are currently underway in the NCI Center for Cancer Research’s Pediatric Oncology Branch:

In addition, the Children’s Oncology Group (COG) and the Pediatric Brain Tumor Consortium are evaluating targeted therapies for selected childhood cancers, including:

  • Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults with Stage IIB or Stage IIIB–IVB Hodgkin Lymphoma (NCT02166463)
  • Selumetinib in Treating Young Patients with Recurrent or Refractory Low-Grade Glioma (NCT01089101)
  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (NCT02883049)
  • Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma (NCT03126916)

In 2017, NCI and COG launched the NCI-COG Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH) trial, which is testing molecularly targeted therapies in children with advanced cancers that are not responding to treatment. Tumor DNA sequencing is being used to identify those children whose cancers have a genetic abnormality that is targeted by a drug being studied in the trial.

NCI Research Funding Decisions

NCI does not make research funding decisions based on predetermined targets for a specific disease area or research category. Rather, the institute relies heavily on highly trained scientists from outside NCI, including experts in pediatric cancer, to review research proposals and judge them on factors such as scientific merit, potential impact, and likelihood of success. Research proposals are also further evaluated by NCI leadership to consider additional factors, such as public health significance, scientific novelty, and overall representation of the research topic within the NCI portfolio. This intensive approach ensures that NCI supports the best science to meet the needs of patients.

NCI uses a number of award mechanisms to support the best scientific proposals through a rigorous grant application and the peer review process. The vast majority of NCI funding opportunities are focused on research areas and approaches that are neither disease nor population specific. These solicitations encourage proposals in a variety of scientific areas key to advancing cancer research for children and adults alike.

FDA-Approved Drugs for Childhood Cancer

Since 1990, the Food and Drug Administration has approved twelve drugs for childhood cancers, and data from NCI-sponsored clinical trials were used to support the approvals of several of these drugs (marked by asterisks):

Drug Name Childhood Cancer Year Approved
Teniposide acute lymphoblastic leukemia 1992
Pegaspargase * acute lymphoblastic leukemia 1994 and 2006
Clofarabine acute lymphoblastic leukemia 2004
Nelarabine * T-cell acute lymphoblastic leukemia 2005
Imatinib *

chronic myeloid leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia

Everolimus subependymal giant cell astrocytoma (SEGA) 2010 and 2012
Asparaginase Erwinia chrysanthemi * acute lymphoblastic leukemia 2011
Dinutuximab (monoclonal antibody ch14.18)* neuroblastoma 2015
Avelumab Merkel cell carcinoma (in patients age 12 and older) 2017
Pembrolizumab *

refractory classic Hodgkin lymphoma

mismatch repair deficient and microsatellite instability-high solid tumors

Nivolumab mismatch repair deficient and microsatellite instability-high colorectal cancer (in patients age 12 and older) 2017
Ipilimumab melanoma (in patients age 12 and older) 2017