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Nrf2/p-Fyn/ABCB1 axis accompanied by p-Fyn nuclear accumulation plays pivotal roles in vinorelbine resistance in non-small cell lung cancer

Tamari, Shigeyuki 京都大学 DOI:10.14989/doctor.k24508

2023.03.23

概要

Lung cancer is the leading cause of cancer‑related mortality
worldwide (1). Cisplatin‑vinorelbine is a standard adjuvant
chemotherapy for patients with resected stage II and III
non‑small cell lung cancer (2). Adjuvant cisplatin‑vinorelbine
treatment has been shown to improve the overall survival
rate by 8.9% and the disease‑free survival rate by 9.2% at 5
years (3). The 5‑year survival rate is, however, unsatisfactory
at 40.6% for patients with p‑stage IIA, 41.1% for IIB and
28.3% for IIIA (4). Chemotherapeutic failure occurs owing to
resistance to chemotherapeutic agents, which remains a chal‑
lenge in cancer treatment (5). The development of resistance
is associated with the overexpression of energy‑dependent
drug efflux pumps, known as the ATP‑binding cassette (ABC)
family of proteins, which eject anticancer drugs from cells (6).
Activated ABC sub‑family B member 1 (ABCB1) is commonly
associated with drug resistance (7,8).
The overexpression of ABCB1 and the activation of
phosphorylated Fyn (p‑Fyn) play a crucial role in vinorel‑
bine resistance, and integrin β3 functions as an upstream
regulator of Src family kinases (SFKs), including Fyn, in
vinorelbine‑resistant (VR) cells (9). ...

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