Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells

Overview

Journal Mol Cancer Ther

Date 2023 Oct 6

PMID 37802502

Authors

Soichi Hirai

Tadaaki Yamada

Yuki Katayama

Masaki Ishida

Hayato Kawachi

Yohei Matsui

Ryota Nakamura

Kenji Morimoto

Mano Horinaka

Toshiyuki Sakai

Yoshitaka Sekido

Shinsaku Tokuda

Koichi Takayama

Affiliations

Soon will be listed here.

Abstract

Few treatment options exist for pleural mesothelioma (PM), which is a progressive malignant tumor. However, the efficacy of molecular-targeted monotherapy is limited, and further therapeutic strategies are warranted to treat PM. Recently, the cancer cell-cycle checkpoint inhibitors have attracted attention because they disrupt cell-cycle regulation. Here, we aimed to establish a novel combinational therapeutic strategy to inhibit the cell-cycle checkpoint kinase, ATR in PM cells. The siRNA screening assay showed that anexelekto (AXL) knockdown enhanced cell growth inhibition when exposed to ATR inhibitors, demonstrating the synergistic effects of the ATR and AXL combination in some PM cells. The AXL and ATR inhibitor combination increased cell apoptosis via the Bim protein and suppressed cell migration when compared with each monotherapy. The combined therapeutic targeting of AXL and ATR significantly delayed regrowth compared with monotherapy. Thus, optimal AXL and ATR inhibition may potentially improve the PM outcome.

Citing Articles

Targeted Therapy in Mesotheliomas: Uphill All the Way.

Bertoli E, De Carlo E, Bortolot M, Stanzione B, Del Conte A, Spina M Cancers (Basel). 2024; 16(11).

PMID: 38893092 PMC: 11171080. DOI: 10.3390/cancers16111971.

Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma.

Yun K, Bazhenova L Cancers (Basel). 2024; 16(7).

PMID: 38610930 PMC: 11011044. DOI: 10.3390/cancers16071252.

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