Gender and Sex-Related Differences in Normal Tissue Effects Induced by Platinum Compounds

Abstract

Gender medicine in the field of oncology is an under-researched area, despite the existing evidence towards gender-dependent response to therapy and treatment-induced adverse effects. Oncological treatment aims to fulfil its main goal of achieving high tumour control by also protecting normal tissue from acute or chronic damage. Chemotherapy is an important component of cancer treatment, with a large number of drugs being currently in clinical use. Cisplatin is one of the most commonly employed chemotherapeutic agents, used either as a sole drug or in combination with other agents. Cisplatin-induced toxicities are well documented, and they include nephrotoxicity, neurotoxicity, gastrointestinal toxicity, ototoxicity, just to name the most frequent ones. Some of these toxicities have short-term sequelae, while others are irreversible. Furthermore, research showed that there is a strong gender-dependent aspect of side effects caused by the administration of cisplatin. While evidence towards sex differences in animal models is substantial, clinical studies considering sex/gender as a variable factor are limited. This work summarises the current knowledge on sex/gender-related side effects induced by platinum compounds and highlights the gaps in research that require more attention to open new therapeutic possibilities and preventative measures to alleviate normal tissue toxicity and increase patients’ quality of life in both males and females.

Estradiol protects hair cells from cisplatin-induced ototoxicity via Nrf2 activation

“…Gender differences in cisplatin ototoxicity have been reported [ 12 , 24 ]. Sex hormones, particularly estrogen, are thought to have protective effects against hair cell loss in female patients [ 24 ].…”

“…Gender differences in cisplatin ototoxicity have been reported [ 12 , 24 ]. Sex hormones, particularly estrogen, are thought to have protective effects against hair cell loss in female patients [ 24 ]. However, the mechanism by which E2 protects against cisplatin-induced hair cell loss is not well understood.…”

Bias and Class Imbalance in Oncologic Data—Towards Inclusive and Transferrable AI in Large Scale Oncology Data Sets

“…There is increasing awareness of bias and class imbalance sources in medical data sets. Notably, gender [ 16 , 17 ] and race bias [ 18 , 19 ] with class imbalances are increasingly highlighted in the literature. Both factors have been shown to affect outcomes.…”

The Next Frontier in Health Disparities—A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back

“…Retrospective and prospective studies have previously identified potential prognostic and predictive factors grounded in sex differences. Sex differences have been noted in anti-epileptic management [ 70 ], chemotherapy [ 12 , 71 ], and immunotherapy [ 11 , 17 ] ( Table 3 ). Looking ahead at the potential future results of omic analyses will therefore involve looking back at current and previous trials wherein a biospecimen was/is being collected to examine where future conclusions may originate from ( Table 5 ) and how this bedside data connects to bench data, including tissue culture and animal studies.…”

“…In the context of glioma, several papers have explored biological factors and sex-dependent differences between men and women and implications related to histology, sex hormones [ 8 , 9 ], pregnancy, menstruation, menopause, and oral contraceptives. There is, however, an ongoing lack of in-depth understanding of the physiology and metabolism that underpins sex differences in glioma, with data just emerging [ 3 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. These biological differences can result in differences in the clinical outcomes of novel interventions.…”