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Tumor Immunotherapy

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Related Experiment Video

Updated: May 21, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Immune Checkpoint Inhibitor Therapy for Aggressive Pituitary Neuroendocrine Tumors.

Andrew L Lin1,2,3, Vasilisa Rudneva4, Adam Newton2

  • 1Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

The Journal of Clinical Endocrinology and Metabolism
|March 20, 2025
PubMed
Summary

Immune checkpoint inhibitors (ICIs) show safety and feasibility for aggressive pituitary neuroendocrine tumors (PitNETs). Mismatch repair deficiency (MMRd) and temozolomide hypermutation may predict response to ICI therapy in PitNET patients.

Keywords:
biomarkersclinical trialsimmunotherapypituitary neuroendocrine tumors

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Area of Science:

  • Oncology
  • Immunotherapy
  • Genetics

Background:

  • Pituitary neuroendocrine tumors (PitNETs) progressing after surgery and radiotherapy require novel therapeutic strategies.
  • The efficacy and predictive biomarkers for immune checkpoint inhibitors (ICIs) in PitNETs remain largely uncharacterized.

Purpose of the Study:

  • To assess the feasibility and activity of combined ipilimumab and nivolumab in PitNET patients.
  • To identify potential genetic biomarkers predictive of response to ICI therapy in PitNETs.

Main Methods:

  • A prospective, single-center, phase 2 clinical trial was conducted using ipilimumab and nivolumab for PitNET patients.
  • Objective response was evaluated using iRANO criteria, with genetic biomarker analysis performed on tumor samples.

Main Results:

  • No objective responses were observed in the 9 evaluable patients, though 2/9 experienced tumor shrinkage.
  • Mismatch repair deficiency (MMRd) and temozolomide hypermutation were associated with immunological response in a biomarker cohort.
  • Analysis of tumors before and after ICI treatment revealed evidence of immunoediting, including loss of MMRd and decreased tumor mutational burden.

Conclusions:

  • ICI treatment, including ipilimumab and nivolumab, is safe and feasible for aggressive PitNETs.
  • MMRd and temozolomide hypermutation are identified as potential biomarkers for predicting ICI response in PitNETs.
  • ICIs represent a potential additional treatment option for PitNETs, warranting further investigation in larger studies.