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Published on: November 5, 2020
Promising targetable biomarkers in pancreatic neuroendocrine tumours
M Borghesani1, L Gervaso1,2, C A Cella1
1Division of Gastrointestinal and Neuroendocrine Cancer Medical Treatment, European Institute of Oncology, Milano, IT, Italy.
Introduction:
In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development.
Areas Covered:
We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs.
Expert Opinion:
Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.
Insights
Targeted therapies for Pancreatic Neuroendocrine Tumors (PanNETs) show promise but face challenges due to rarity and patient heterogeneity. Improved patient selection and efficacy measures are crucial for advancing PanNETs treatment.
Area of Science:
- Oncology
- Translational Medicine
- Biomarker Discovery
Background:
- Pancreatic Neuroendocrine Tumors (PanNETs) lack effective targeted therapies due to their rarity and heterogeneity.
- Existing targeted treatments have shown disappointing efficacy in early clinical trials.
Purpose of the Study:
- To review promising druggable biomarkers and potential targeted therapies for PanNETs.
- To identify challenges and propose solutions for developing effective PanNETs treatments.
Main Methods:
- Literature review of early-phase clinical trials for PanNETs treatments.
- Identification of six key therapeutic targets: Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR.
Main Results:
- Six promising targets identified, but reported efficacy outcomes are disappointing.
- Reasons for poor outcomes include patient heterogeneity, lack of biomarker selection, and poor understanding of interfering mechanisms.
Conclusions:
- Targeted therapy development for PanNETs lags behind other cancers.
- Crucial need for better patient selection (topography, grading, biomarkers) to optimize targeted therapy efficacy.
- Alternative efficacy assessment methods are needed for indolent NETs.
