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Published on: February 25, 2020
Immune therapy-related hyperprogressive disease: Molecular mechanisms, biomarkers, and clinical strategies
Xiao-Ming Zhang1,2, Fei-Yu Zhao3, Lin-Feng Gao2
1Department of Thoracic Oncology, Respiratory and Critical Care Medicine, The Eighth Medical Center of People's Liberation Army General Hospital, Beijing 100091, China.
Abstract:
Programmed death receptor-1 inhibitors have significantly improved the prognosis of various malignancies. Nevertheless, hyperprogressive disease (HPD), recognized as a severe adverse reaction to immunotherapy, causes a substantial surge in tumor burden and notably shortens the survival of 4%-29% of patients. This article comprehensively reviews the controversies regarding the clinical definition of HPD, its cross-cancer epidemiological features (encompassing gastric cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, etc.), and potential molecular mechanisms (such as MDM2/MDM4 gene amplification, EGFR mutations, and reprogramming of the immune microenvironment). It further delves into biomarker-based predictive models, targeted combination therapy strategies, and salvage treatment alternatives. Ultimately, it puts forward future directions, including the establishment of a multicenter HPD registry database and organoid predictive models, aiming to offer evidence-based guidance for clinical practice.
Insights
Hyperprogressive disease (HPD) is a severe immunotherapy side effect that worsens outcomes for cancer patients. This review clarifies HPD definitions, mechanisms, and treatment strategies for better clinical guidance.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Programmed death receptor-1 (PD-1) inhibitors have transformed cancer treatment.
- Hyperprogressive disease (HPD) is a serious adverse event associated with immunotherapy.
- HPD significantly increases tumor burden and reduces survival in 4%-29% of patients.
Purpose of the Study:
- To comprehensively review the clinical definition, epidemiology, and molecular mechanisms of HPD.
- To explore biomarker-based predictive models and therapeutic strategies for HPD.
- To propose future research directions for managing HPD.
Main Methods:
- Literature review of HPD definition controversies and epidemiological features across various cancers.
- Analysis of potential molecular mechanisms, including gene amplification and immune microenvironment alterations.
- Evaluation of predictive models, combination therapies, and salvage treatments.
Main Results:
- HPD presents significant challenges in clinical definition and diagnosis.
- Potential molecular drivers include MDM2/MDM4 amplification and EGFR mutations.
- Immune microenvironment reprogramming is implicated in HPD development.
Conclusions:
- Further research is needed to standardize HPD definition and improve prediction.
- Developing targeted combination therapies and salvage treatments is crucial.
- Establishing multicenter registries and organoid models will guide clinical practice.
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