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Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

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Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.

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Accelerating Drug Development for Neuroblastoma: Consensus Statement From the Third Neuroblastoma Drug Development

Steven G DuBois1, Lucas Moreno2, John Anderson3

  • 1Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.

Pediatric Blood & Cancer
|June 13, 2025
PubMed
Summary

High-risk neuroblastoma remains a deadly childhood cancer. Experts prioritized novel GD2-directed therapies, combinations, and CAR-T cells to improve patient outcomes and overcome drug development challenges.

Keywords:
ALKATRB7‐H3EZH2GD2GPC2MYCNclinical trialsdrug developmentneuroblastomarelapse

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Area of Science:

  • Pediatric Oncology
  • Cancer Drug Development
  • Immunotherapy

Background:

  • High-risk neuroblastoma has a poor prognosis, with ~50% cure rates despite existing treatments.
  • Significant advancements in identifying therapeutic targets and combination strategies are needed.
  • International Neuroblastoma Drug Development Strategy (NDDS) meetings convene stakeholders to guide research.

Purpose of the Study:

  • To prioritize agents and address challenges in high-risk neuroblastoma drug development.
  • To identify promising novel GD2-directed therapies and combination strategies.
  • To discuss barriers to clinical trial drug access and propose solutions.

Main Methods:

  • Multistakeholder meeting (academia, industry, regulatory, patient advocacy) to prioritize agents.
  • Review of current data to prioritize or deprioritize targets and agents.
  • Discussion of strategies to improve access to investigational drugs for clinical trials.

Main Results:

  • Prioritized novel GD2-directed combinations (e.g., with EZH2, IL15, TIGIT) and GD2-directed chimeric antigen receptor (CAR)-T cells.
  • Identified emerging CAR-T targets (B7-H3, GPC2) and high-priority targeted therapy combinations (e.g., Aurora A kinase with BCL2 or ATR inhibitors).
  • Recognized drug access for clinical trials as a major barrier, emphasizing collaborative efforts and early regulatory engagement.

Conclusions:

  • Combination therapies, including novel GD2-directed approaches and targeted agents, are crucial for improving frontline treatment of high-risk neuroblastoma.
  • Addressing challenges in drug access through international collaboration and early regulatory interaction is essential for accelerating therapeutic progress.
  • Continued strategic prioritization of agents and targets is vital for advancing neuroblastoma drug development.