C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors

Riccardo Ricci, Francesco Pierconti, Alessandra Cassano, Emilio Bria, Giampaolo Tortora, Luigi Maria Larocca, Maurizio Martini, Antonia Strippoli, Alessandra Cocomazzi, Michele Basso, Tonia Cenci, Vincenzo Fiorentino, Carlo Antonio Barone, Lucia Ricci-Vitiani

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Alterations in the transcriptional factor c-MYC could be involved in the anti-EGFR resistance in metastatic colorectal cancer (mCRC). The c-MYC expression was evaluated in 121 RAS and BRAF wild-type mCRC before treatment with anti-EGFR+Folfiri therapy and in 33 subsequent metastases collected during target therapy (TT) or in TT resistance phase. We analyzed the expression and the functional role of some c-MYC linked miRNAs (miR-31-3p, miR-143 and miR-145) in our patient group and in two CRC cell lines, also performing a c-MYC target PCR array. Patients with higher c-MYC expression (HME) showed a significant lower PFS and OS when compared to those with low c-MYC expression (LME). HME pattern was significantly more frequent in the metastases after TT and significantly associated to anti-EGFR molecular resistance alterations. We also found a significant correlation between the expression of the above-mentioned c-MYC linked miRNAs, c-MYC level and anti-EGFR resistance. Moreover, expression gene profiling pointed out the pivotal role of c-MYC in CRC-related cell-cycle, apoptosis, signal transduction and cell-growth pathways. c-MYC expression might distinguish patients with a lower PFS and OS in anti-EGFR treated mCRC. The individuation of some miRNAs involved in the c-MYC pathway regulation and the downstream c-MYC effector genes could provide a new possible target to overcome the anti-EGFR resistance in mCRC.
Original languageEnglish
Pages (from-to)638-656
Number of pages19
JournalCancers
Volume12
DOIs
Publication statusPublished - 2020

Keywords

  • C-MYC
  • Colorectal cancer
  • EGFR inhibitor resistance
  • Targeted therapy

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