key: cord-0962946-i4pb4u6j
authors: Hayashi, Takuma; Konishi, Ikuo
title: Cancer therapy with decreased SARS-CoV-2 infection rates in cancer patients
date: 2021-12-30
journal: Br J Cancer
DOI: 10.1038/s41416-021-01685-3
sha: 0b42f55b81f0e7526ec3d33d80cc2188fcd8040a
doc_id: 962946
cord_uid: i4pb4u6j

nan

innate immune response-related signaling pathways [4] . A Study of the activated signaling responses at all time points revealed that MERS-CoV infection regulates a broad range of cellular functions, including the PI3K/AKT/mTOR signaling pathways [4] .

Of particular interest in the SARS-CoV-2 life cycle is its modulation of the mTOR molecule and its pathways. Importantly, the mTOR signaling pathway is necessary for viral translation during the SARS-CoV-2 life cycle [5] . To ensure the replication of coronavirus, SARS-CoV-2 infection reportedly causes activation of mTOR/PI3K signals. Hepatocyte Nuclear Factor 1 (HNF1) family, which is not included in the mTOR/PI3K signaling pathway, markedly induces the expression of ACE2 gene [6, 7] . Presumably, mTOR/PI3K signal activation may be a change in cellular function that occurs after SARS-CoV-2 infection rather than inducing ACE2 gene expression. Therefore, it seems that the rates of SARS-CoV-2 positivity and the attendant severity of COVID-19 will be lower in cancer patients who received antineoplastic agents that suppress the mTOR/PI3K signaling pathway as compared to cancer patients administered other antineoplastic agents (Fig. 1) .

Recent studies have shown that a subset of the approved kinase inhibitors targeting the extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways significantly inhibited coronavirus replication, including SARS-CoV-2, whether they were administered before or after the viral infection was established. In clinical settings, mTOR/PI3K inhibitors (everolimus, temsirolimus and alpelisib), other kinase inhibitors (dasatinib and crizotinib) and antimetabolites (decitabine and gemcitabine) are prescribed as antineoplastic agents to patients with cancer. Thus, antineoplastic agents inhibiting the activity of ERK/MAPK or PI3K/AKT/mTOR are not only suppressing malignant tumour growth but also mitigating the severity of cancer patients with SARS-CoV-2 infection by inhibiting SARS-CoV-2 replication (Fig. 1) . Patients with cancer who received antineoplastic agents that inhibit the mTOR/PI3K signaling pathway might exhibit a statistically significant reduction in SARS-CoV-2 positivity rates and correspondingly lower rates of COVID-19 severity. Taken together, from the perspective of preventing the severity of COVID-19 and treating cancer patients infected with SARS-CoV-2, it is important to consider the therapeutic effects of mTOR inhibitors, other kinase inhibitors, or DPP4 inhibitors because of their inhibitory properties on the mTOR/PI3K signaling pathway.

The material (manuscript and figure) is original research. It has not been previously published and has not been submitted for publication elsewhere while under consideration.

This manuscript is an editorial and does not contain research data. Therefore, there is no research data or information to be published or opened. Activation of the mTOR/PI3K signaling pathway in the host cell contributes to the viral life cycle from gene transcription to mRNA translation into proteins and subsequent assembly/budding of SARS-CoV-2. Additionally, mTOR/PI3K signaling pathway promotes replication and proliferation of cancer cells. Therefore, antineoplastic agents that inhibit the mTOR/PI3K pathway does not only suppress the growth of cancer cells but also inhibit the replication of SARS-CoV-2. AKT protein kinase B-alpha, mTOR mammalian target of rapamycin, PI3K phosphoinositide 3-kinase, RTK receptor tyrosine kinase, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.

Association of antineoplastic therapy with decreased SARS-CoV-2 infection rates in patients with cancer

The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike

Thermodynamic equilibrium dose-response models for MERS-CoV infection reveal a potential protective role of human lung mucus but not for SARS-CoV-2

Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis

mTOR inhibition in COVID-19: a commentary and review of efficacy in RNA viruses

Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus

ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes

We thank all the medical staff and co-medical staff for providing and helping medical research at National Hospital Organization Kyoto Medical Center. We appreciate Crimson Interactive Japan Co., Ltd. for revising and polishing our manuscript in the native English language. 

The authors declare no competing interests.

Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41416-021-01685-3.Correspondence and requests for materials should be addressed to Takuma Hayashi.Reprints and permission information is available at http://www.nature.com/ reprints