This study examines the biological influences of sex on cancer treatment.

Differences in cancer incidence between the sexes are thought to result, in part, from hormonal differences, but the topic has not been studied in much detail. The underlying molecular mechanisms responsible remain poorly understood, and current approaches to medication and treatment protocols use genetic data to assign therapies without considering factors related to sex differences. 

Despite this, some treatments, such as chemotherapy, show clear gender-related disparities in response rates and side effects. This article, published in the journal Current Research in Pharmacology and Drug Discovery, analyzes the influence of sex as a biological variable in oncology.

Sex Differences in Mortality 

Overall cancer mortality is higher in men, especially in hematological malignancies. The difference in cancer incidence between the sexes is thought to be regulated genetically, molecularly, and by sex hormones. Additionally, gene polymorphisms can result in variations in cancer incidence. Sex hormone differences may be one of the reasons why men experience a higher risk of developing acute lymphocytic leukemia, as estrogen suppresses nuclear factor kappa B. Estrogen is also directly related to a higher incidence of thyroid carcinoma in women by promoting thyroid cancer cell growth and resistance to apoptosis. 

Differences in Immune Response

The immune response disparities between the sexes can also influence cancer outcomes. These are primarily the result of genetic mediators, such as sex chromosomes; hormonal mediators; environmental mediators, such as the microbiome, and social behaviors, such as smoking and alcohol consumption. Sex hormones can affect dendritic cells, macrophages, and B and T lymphocytes, which can go on to affect the immune response to cancer. In many cases, women have a more robust immune response, which has the side effect of causing more autoimmune conditions.

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Differences in Medication Response

Regarding medications, women experience more adverse effects when taking cytostatic drugs. Some sex-specific adverse effects have been found in drugs such as ifosfamide, which can cause neurotoxicity in females. 

Due to the sex differences discussed in this study, the authors note the importance of including them as an area of study in clinical trials. Women tend to be underrepresented in clinical trials, and their increased participation can result in more accurate and appropriate therapy development. Additional research is needed to gain a comprehensive understanding of the fundamental processes behind these sex differences so that they can be addressed more fully in future medication development and therapies.

Source: 

Rakshith, H., Lohita, S., Rebello, A. P., Goudanavar, P., & Naveen, N. R. (2023). Sex differences in drug effects and/or toxicity in oncology. Current Research in Pharmacology and Drug Discovery, 4, 100152. https://doi.org/10.1016/j.crphar.2022.100152

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