Tumor mutational burden as a potential biomarker for immunotherapy in pancreatic cancer: Systematic review and still-open questions

Rita T. Lawlor, Paola Mattiolo, Andrea Mafficini, Seung Mo Hong, Maria L. Piredda, Sergio V. Taormina, Giuseppe Malleo, Giovanni Marchegiani, Antonio Pea, Roberto Salvia, Valentyna Kryklyva, Jae Il Shin, Lodewijk A. Brosens, Michele Milella, Aldo Scarpa, Claudio Luchini

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-mo-lecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

Original languageEnglish
Article number3119
JournalCancers
Volume13
Issue number13
DOIs
Publication statusPublished - 2021 Jul 1

Bibliographical note

Funding Information:
This study is supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182); Fondazione Cariverona: Oncology Biobank Project ?Antonio Schiavi? (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001); Italian Ministry of Health (RF CO-2019-12369662: CUP: B39C21000370001).

Funding Information:
Funding: This study is supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182); Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi” (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001); Italian Ministry of Health (RF CO-2019-12369662: CUP: B39C21000370001).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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