The DNA damage response and autophagy during cancer development: an antagonistic pleiotropy entanglement

ABSTRACT

The DNA damage response (DDR) pathway is a cardinal cellular stress response mechanism that during cancer development follows an antagonistic pleiotropy mode of action. Given that DDR activation is an energy demanding process, interplay with macroautophagy/autophagy, a stress response and energy providing mechanism, is likely to take place. While molecular connections between both mechanisms have been reported, an open question regards whether autophagy activation follows solely or is entangled with DDR in a similar antagonistic pleiotropy pattern during cancer development. Combing evidence on the spatiotemporal relationship of DDR and autophagy in the entire spectrum of carcinogenesis from our previous studies, we discuss these issues in the current addendum.

Abbreviation: AMPK: AMP-dependent protein kinase; DDR: DNA damage response.

KEYWORDS:

• Disease
• genomic instability
• macroautophagy
• stress
• tumor

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the National Institute of General Medical Sciences [GM131919]; National Public Investment Program of the Ministry of Development and Investment/General Secretariat for Research and Technology, in the framework of the Flagship Initiative to address SARS-CoV-2 (2020ΣΕ01300001); Sonia Kotopoulos donation.