Sertraline-induced melanoma – second case in the world literature: focus on the (photo) nitroso contamination of the drug as generator for phototoxicity and photocarcinogenicity in humans
Medical Review (Med. pregled), 2026, 62(2), 52-59.
G. Tchernev1,2, L. Ivanov1, D. S. Krastev3,4, N. S. Krastev5,6, K. G. Tchernev Jr1, R. Hasegawa6, S. Kordeva1
1Onkoderma – Clinic for Dermatology, Venereology and Dermatologic Surgery – Sofia
2Department of Dermatology and Venereology, Medical Institute of Ministry of Interior– Sofia
3College of Medicine “Yordanka Filaretova”, Medical University – Sofia
4Department of Anatomy and Physiology, South-West University “Neofit Rilski” – Blagoevgrad
5Department of Anatomy, Faculty of Medicine, Medical University – Sofia
6Sofia University “Sv. Kliment Ohridski”
Abstract: The link between the onset and progression of cutaneous melanoma relates not only to the currently known photocarcinogenesis, but also to the newer and more modern concept involving the notion of nitrosogenesis/carcinogenesis mediated by drugs. Nitrosogenesis of skin cancer is due to carcinogens contained in drugs, also known as nitrosamines. Due to the fact that, according to the literature, these contaminants are also phototoxic substances (regardless of their carcinogenic potency), there are serious indications for the creation of new medical terms such as: drug-mediated photo-nitrosogenesis, and hence photo-nitrosocarcinogenesis of skin cancer. In the broader context of considerations, this also includes newly introduced terms such as onco-pharmacogenesis or pharmaco-oncogenesis, or skin cancer resulting from medication use. Nitrosamines, found as contaminants in more than 90-95% of drugs worldwide, could also be the main cause of phototoxicity in serious doses, which manifests itself in the context of drug use and leads to skin cancer. Nitrosamines are phototoxic due to the instability of their nitroso group, when exposed to ultraviolet light. In addition, a large percentage of them are also carcinogenic, mutagenic, or genotoxic substances. The overlap between the lists of phototoxic drugs worldwide (from the time when photocontamination with nitrosamines was not known) and those of the FDA (from 2018) regarding those affected by nitrosamine/photocarcinogen contamination indicates that phototoxicity is most probably specifically or primarily due to them. At the same time, the literature on the subject is growing exponentially and drawing the attention of the scientific community to the following: the intake of drugs contaminated with photocarcinogens leads to the development of melanoma (but also keratinocyte cancers), with the degree of potential contamination and the number of potentially contaminated drugs taken correlating with the severity of the cancer: the tendency to recur, the number of tumors, and the thickness of the tumor. The tests used by regulators to determine pure carcinogenicity in bacteria (Ames test) and rodents (CPCA test) do not actually determine cumulative phototoxicity and subsequent photocarcinogenicity in humans, which is essentially the reason for their ineffectiveness/limited objectivity or explanation of the recent dilemma: “Why does prolonged use of nitrosamine-contaminated drugs in all likelihood cause pho-totoxicity and photocarcinogenicity even at doses tolerated by regulators or determined by them to be safe?” The rhetorical question remains: “Is this the reason why regulatory authorities refuse to disclose and currently do not disclose the nor-mal concentrations of photocarcinogens present in drugs?” The so-called ʺdynamic carcinogenesisʺ in humans, particularly with regard to skin cancer, is multifacto-rial and cannot be equated with direct carcinogenesis in bacteria or rodents under laboratory conditions. The regulatory tests do not definitively determine cumulative phototoxicity in humans based on the intake of the relevant nitrosamine. How would one interpret the fact that nitrosamine intake is not carcinogenic but is phototoxic and subsequently carcinogenic? Elimination regimens for photocarcinogens, also known as nitrosamines, should become a priority. In this context, we present a sec-ond case in the world literature of a patient who developed cutaneous melanoma relatively soon after taking the antidepressant sertraline. This example is further evidence of the discrepancies between the carcinogenic potency of nitrosamines in drugs (determined on the basis of static carcinogenicity tests in laboratory condi-tions) and the actual cumulative phototoxicity/photocarcinogenicity in the conditions of the so-called dynamic human carcinogenesis.
Key words: drug-mediated photocarcinogenesis, drug-related nitrosocarcinogenesis, cutaneous melanoma, dermatologic surgery, sertraline-induced skin cancer, phototoxicity, photocarcinogenicity, nitrosamines, photocarcinogens
Address for correspondence: Prof. Georgi Tchernev, MD, e-mail: georgi_tchernev@yahoo.de