Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers

Olawale Razaq Ajuwon; Fleury Augustine Nsole-Biteghe; Jean Delacroix Ndong; Lester Merlin Davids; Basiru Olaitan Ajiboye; Bartholomew Brai; Fisayo Abraham Bamisaye; John Adeolu Falode; Ikenna Maximillian Odoh; Kabirat Iyabode Adegbite; Bosede Oluwasayo Adegoke; Monde Ntwasa; Sogolo Lucky Lebelo; Ademola Olabode Ayeleso

doi:10.2147/OTT.S457749

Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers

Onco Targets Ther. 2024 Aug 5:17:605-627. doi: 10.2147/OTT.S457749. eCollection 2024.

Authors

Olawale Razaq Ajuwon¹, Fleury Augustine Nsole-Biteghe², Jean Delacroix Ndong³, Lester Merlin Davids⁴, Basiru Olaitan Ajiboye¹, Bartholomew Brai¹, Fisayo Abraham Bamisaye¹, John Adeolu Falode¹, Ikenna Maximillian Odoh^{1

5}, Kabirat Iyabode Adegbite⁶, Bosede Oluwasayo Adegoke⁷, Monde Ntwasa⁸, Sogolo Lucky Lebelo⁸, Ademola Olabode Ayeleso^{8

9}

Affiliations

¹ Department of Biochemistry, Federal University, Oye-Ekiti, Ekiti State, Nigeria.
² Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA, USA.
³ School of Arts and Science, Rutgers University, New Brunswick, NJ, 08901, USA.
⁴ Graduate School of Business, University of Cape Town, Cape Town, South Africa.
⁵ Medical Center, Federal University, Oye-Ekiti, Ekiti-State, Nigeria.
⁶ Department of Environmental Health Science, College of Basic Medical and Health Sciences, Fountain University, Osogbo, Osun State, Nigeria.
⁷ Department of Chemical Pathology, Ekiti State University, Ado-Ekiti, Ekiti State, Nigeria.
⁸ Department of Life and Consumer Sciences, University of South Africa, Florida Park 1709, Roodeport, South Africa.
⁹ Biochemistry Programme, Bowen University, Iwo, Osun State, Nigeria.

Abstract

Photodynamic therapy (PDT) is a groundbreaking approach involving the induction of cytotoxic reactive oxygen species (ROS) within tumors through visible light activation of photosensitizers (PS) in the presence of molecular oxygen. This innovative therapy has demonstrated success in treating various cancers. While PDT proves highly effective in most solid tumors, there are indications that certain cancers exhibit resistance, and some initially responsive cancers may develop intrinsic or acquired resistance to PDT. The molecular mechanisms underlying this resistance are not fully understood. Recent evidence suggests that, akin to other traditional cancer treatments, the activation of survival pathways, such as the KEAP1/Nrf2 signaling pathway, is emerging as an important mechanism of post-PDT resistance in many cancers. This article explores the dual role of Nrf2, highlighting evidence linking aberrant Nrf2 expression to treatment resistance across a range of cancers. Additionally, it delves into the specific role of Nrf2 in the context of photodynamic therapy for cancers, emphasizing evidence that suggests Nrf2-mediated upregulation of antioxidant responses and induction of drug efflux transporters are potential mechanisms of resistance to PDT in diverse cancer types. Therefore, understanding the specific role(s) of Nrf2 in PDT resistance may pave the way for the development of more effective cancer treatments using PDT.

Keywords: Nrf2; antioxidant response; oxidative stress; photodynamic therapy; tumor resistance.

Publication types

Review

Grants and funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Article Processing Charge for publication was paid by University of South Africa, Pretoria, South Africa.