There is significant inter-individual variability in the prevalence and severity of cisplatin-induced ototoxicity, which is greatly influenced by genetic and non-genetic factors that predispose the patient to the development of hearing loss. Currently, the focus should be on identifying patients who are more likely to develop ototoxicity based on genetic and non-genetic factors, as therapies to combat ototoxicity are limited or still under study. The severity of hearing loss and the time of its onset may be influenced by certain genetic polymorphisms or the dose administered, age, sex, diet, the administration of other drugs with ototoxic potential, and association with radiotherapy of the head and neck. Knowing the risk factors allows the doctor to manage each case in a personalized manner, preventing hearing damage, especially in the long term. With the help of PubMed and Scopus, we searched for relevant studies documenting the genetic and non-genetic risk in patients treated with cisplatin. This review article is a synthesis of the literature that points out the importance of these factors, encouraging genetic screening and improving quality of life in patients treated with cisplatin.

Although cisplatin plays a vital role in chemotherapy protocols, its impact on hearing should not be overlooked. The ototoxic effects of cisplatin can lead to hearing loss. Childhood hearing loss can significantly impact various aspects of development. Understanding the mechanism of cisplatin-induced ototoxicity is crucial due to its high level of complexity. The process involves multiple interconnected steps, ranging from cisplatin absorption to its interaction with the cellular antioxidant defense system, nuclear DNA, mitochondria, and the cytokine cascade. Each of these interactions contributes to the overall pathophysiology of ototoxicity and is closely interrelated. Based on these, various hypotheses and conclusions were outlined, and we tried to analyze them as broadly as possible. Knowledge of these mechanisms has given rise to promising avenues and otoprotection strategies to combat ototoxicity. Although there is only one drug approved by the FDA (Food and Drug Administration), there are numerous drugs that target the mechanisms presented, but that need more evidence to be able to be used safely. In addition to these, the role of the multidisciplinary team should not be neglected and protocols should be established for periodic follow-up of patients treated with cisplatin to prevent hearing loss. This narrative review aims to point out all the aspects presented, based on the analysis of the literature and the conclusions drawn over time. We have selected the articles of interest and analyzed the studies that have obtained promising results to bring an overview of how cisplatin acts at the cochlear level, what can be done to combat these mechanisms, what solutions exist now and how we can prevent hearing loss.

Ménière’s disease is a complex disorder of the inner ear, characterized by recurrent episodes of vertigo, progressive hearing loss, tinnitus, and aural fullness. The pathophysiology of this condition is dominated by endolymphatic hydrops, reflecting imbalances in fluid regulation and pressure within the membranous labyrinth, which impair cellular function and the transmission of vestibular and auditory signals. Although genetic predisposition provides a susceptible background, recent studies emphasize that non-genetic factors act as critical triggers of clinical events, determining both the onset of symptoms and the modulation of their severity. These factors directly influence pathophysiology by disrupting endolymphatic homeostasis and altering the intracellular and tissue dynamics of the membranous labyrinth, thereby contributing to the phenotypic variability observed among patients. The key to this process lies in the synergistic interaction between genetic predisposition and external or contextual influences, which determines the threshold at which the compensatory mechanisms of the inner ear fail, triggering the characteristic episodes. Understanding this interdependence, as well as the underlying disease mechanisms, provides essential insights for the identification of preventive and therapeutic strategies aimed not only at symptom control but also at modulating the factors that influence susceptibility to endolymphatic imbalance.

Ménière’s disease is an idiopathic disorder of the inner ear whose causes and pathogenetic mechanisms remain insufficiently elucidated. Advances in genetic analysis technologies have shifted attention toward the role of hereditary components in Ménière’s disease, generating a considerable number of studies investigating the relationship between human genetic variations and disease onset. The results of these investigations highlight the complex and heterogeneous nature of pathogenesis, involving both genetic and epigenetic alterations. Studies have identified multiple candidate genes involved in the regulation of endolymphatic fluid homeostasis, immune response, control of oxidative stress, and maintenance of the structural integrity of the inner ear. However, the reproducibility of these associations varies substantially across populations, reflecting the impact of ethnic heterogeneity, HLA haplotypes, and phenotypic diversity among patients. Moreover, non-genetic factors may act as triggers or modulators of the disease in genetically predisposed individuals. Taken together, the evidence supports a polygenic and context-dependent model of the disorder, in which genes influence susceptibility but do not directly determine disease development. Integrating genomic information with clinical data, analyzing immunological profiles, and investigating exposure to environmental factors are essential steps for patient classification and for the development of individualized treatment strategies.