Hyperprogressive Disease Dynamics in Cancer Immunotherapy
Summary
Hyperprogressive disease (HPD) is an atypical and paradoxical response observed in a subset of patients receiving immune checkpoint inhibitors. Rather than stabilising or reducing tumour burden, treatment triggers an unexpected acceleration of tumour growth, often accompanied by rapid clinical decline. This phenomenon presents a pressing challenge for the clinical community, as conventional imaging criteria may lag behind the true pace of disease evolution. Research to date has highlighted the multifactorial nature of HPD, implicating both tumour‐intrinsic factors such as oncogene amplifications and extrinsic influences stemming from the immune microenvironment. The global significance of HPD lies in its impact on survival and quality of life, emphasising the need for early detection and intervention. Ongoing efforts to delineate risk factors and underlying mechanisms aim to inform patient selection, guide therapeutic combinations and ultimately mitigate the risk of this detrimental outcome.
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Hyperprogressive Disease Dynamics in Cancer Immunotherapy publication trend
The graph below shows the total number of articles in hyperprogressive disease dynamics in cancer immunotherapy across all publications each year (not limited to Nature Index journals).
Technical terms
Hyperprogressive disease (HPD): A rapid acceleration of tumour growth following commencement of immune checkpoint inhibitor therapy, exceeding expected progression rates.
Immune checkpoint inhibitor (ICI): A monoclonal antibody targeting regulatory pathways (e.g. PD-1, PD-L1, CTLA-4) to enhance T-cell-mediated antitumour activity.
Tumour growth kinetics (TGK): A quantitative measure comparing the rate of tumour size change before and after treatment initiation to identify abnormal progression patterns.
Tumour immune microenvironment (TIME): The complex milieu of immune cells, stromal elements and signalling molecules surrounding a tumour that modulates therapeutic response.
Oncogene amplification: An increase in the copy number of a gene whose overexpression can drive malignant transformation and progression.
References
- Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy. Journal of Biomedical Science (2024).
- Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma. npj Precision Oncology (2024).
- Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer. Frontiers in Immunology (2023).
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