Epidermal growth factor receptor mRNA expression: A potential molecular escape mechanism from regorafenib.

Matsusaka, Satoshi; Hanna, Diana L; Ning, Yan; Yang, Dongyun; Cao, Shu; Berger, Martin D.; Miyamoto, Yuji; Suenaga, Mitsukuni; Dan, Shingo; Mashima, Tetsuo; Seimiya, Hiroyuki; Zhang, Wu; Lenz, Heinz-Josef (2020). Epidermal growth factor receptor mRNA expression: A potential molecular escape mechanism from regorafenib. Cancer science, 111(2), pp. 441-450. 10.1111/cas.14273

[img]
Preview
Text
CAS-111-441.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (401kB) | Preview

Regorafenib has improved the survival of patients with refractory metastatic colorectal cancer (mCRC), yet the mechanisms of inherited or acquired resistance are not well understood. A total of 50 patients with refractory mCRC were enrolled. Circulating tumor cell (CTC) enumeration was carried out at baseline, day 21 after initiation of regorafenib, and at the time of progression of disease (PD) using the CellSearch System (Veridex LLC, NJ, USA). Poly(A) mRNA was extracted from CTCs, and gene expression of epithelial and epithelial-mesenchymal transition markers was analyzed by a multiplex-PCR based DNA Chip. Patients with fewer than 3 CTCs at baseline and day 21 had a longer progression-free survival than those with 3 or more CTCs (3.3 vs 2.0 months, P = .008 and 3.3 vs 2.0 months, P = .004, respectively). Patients with fewer than 3 CTCs at baseline and day 21 had a longer overall survival (OS) than those with 3 or more CTCs (10.0 vs 4.6 months, P < .001 and 8.7 vs 3.8 months, P = .003, respectively). In multivariable analysis, CTC counts remained significantly associated with OS at baseline and day 21 (P = .019 and P = .028). Circulating tumor cell EGFR gene expression was upregulated at day 21 and/or PD in 64% of patients. Patients had significantly increased EGFR expression at PD compared to baseline (P = .041) and at day 21 and/or PD compared to baseline (P = .004). Our findings suggest that CTC count and EGFR expression could be useful markers of regorafenib efficacy and outcomes. Upregulation of CTC EGFR expression might be a molecular escape mechanism under regorafenib therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Berger, Martin Dave

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1349-7006

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

27 Apr 2020 07:54

Last Modified:

27 Apr 2020 07:54

Publisher DOI:

10.1111/cas.14273

PubMed ID:

31821662

Uncontrolled Keywords:

circulating tumor cell colorectal cancer epidermal growth factor receptor epithelial marker and EMT regorafenib

BORIS DOI:

10.7892/boris.143028

URI:

https://boris.unibe.ch/id/eprint/143028

Actions (login required)

Edit item Edit item
Provide Feedback