Therapy resistance in neuroblastoma: Mechanisms and reversal strategies
Xia Zhou1, Xiaokang Wang2,3,4, Nan Li5
1Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China.
Abstract:
Neuroblastoma is one of the most common pediatric solid tumors that threaten the health of children, accounting for about 15% of childhood cancer-related mortality in the United States. Currently, multiple therapies have been developed and applied in clinic to treat neuroblastoma including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the resistance to therapies is inevitable following long-term treatment, leading to treatment failure and cancer relapse. Hence, to understand the mechanisms of therapy resistance and discover reversal strategies have become an urgent task. Recent studies have demonstrated numerous genetic alterations and dysfunctional pathways related to neuroblastoma resistance. These molecular signatures may be potential targets to combat refractory neuroblastoma. A number of novel interventions for neuroblastoma patients have been developed based on these targets. In this review, we focus on the complicated mechanisms of therapy resistance and the potential targets such as ATP-binding cassette transporters, long non-coding RNAs, microRNAs, autophagy, cancer stem cells, and extracellular vesicles. On this basis, we summarized recent studies on the reversal strategies to overcome therapy resistance of neuroblastoma such as targeting ATP-binding cassette transporters, MYCN gene, cancer stem cells, hypoxia, and autophagy. This review aims to provide novel insight in how to improve the therapy efficacy against resistant neuroblastoma, which may shed light on the future directions that would enhance the treatment outcomes and prolong the survival of patients with neuroblastoma.
Insights
Neuroblastoma, a common childhood cancer, often develops resistance to therapies. Understanding resistance mechanisms and developing reversal strategies are crucial for improving treatment outcomes in children.
Area of Science:
- Pediatric Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Neuroblastoma is a leading cause of cancer mortality in children.
- Current therapies include chemotherapy, radiotherapy, targeted therapy, and immunotherapy.
- Therapy resistance is a major challenge, leading to treatment failure and relapse.
Purpose of the Study:
- To review mechanisms of neuroblastoma therapy resistance.
- To identify potential molecular targets for overcoming resistance.
- To summarize strategies for reversing neuroblastoma treatment resistance.
Main Methods:
- Literature review of recent studies on neuroblastoma resistance.
- Focus on molecular mechanisms including genetic alterations and dysfunctional pathways.
- Analysis of novel therapeutic targets and reversal strategies.
Main Results:
- Identified key targets such as ATP-binding cassette transporters, long non-coding RNAs, microRNAs, autophagy, cancer stem cells, and extracellular vesicles.
- Summarized reversal strategies involving targeting these mechanisms.
- Highlighted the role of MYCN gene, hypoxia, and autophagy in resistance.
Conclusions:
- Understanding neuroblastoma resistance mechanisms is vital for developing effective treatments.
- Targeting specific molecular pathways offers promising strategies to overcome therapy resistance.
- Further research into these targets can improve outcomes for refractory neuroblastoma patients.
