Carcinogen-induced self-inflicted genome-wide DNA breaks in ‘habit-continued’ oral cancer: A possible survival strategy by cancer cells

Abstract

Despite recent advances in early detection technologies, oral squamous cell carcinoma (OSCC) is mostly detected in advanced stages in low- and middle-income countries. It is commonly observed that due to negligence, patients usually continue tobacco chewing or smoking habits even after the development of OSCC. We coined the term for such cases as ‘habit-continued OSCC’ (HC-OSCC). This situation is highly unique for OSCC as compared to the other malignancies of the body, and persistent exposure to the carcinogens might be lethal to the cancer cells. This paper discussed a novel hypothesis where cancer cells maintain their survival and integrity in HC-OSCC. We propose that cancer cells survive persistent carcinogenic attacks by reversibly increasing genome-wide DNA breaks, thereby limiting premature mitotic progression. This highly orchestrated event is executed by the caspase-activated DNase (CAD) and is governed through phosphorylation by DNA damage response kinase. A possible implication in terms of clinical presentation and therapeutic opportunities has been discussed in detail.