Cancer incidence is on the rise worldwide, posing a rapidly increasing humanitarian and economic challenge. Male and female populations have different cancer susceptibility and survival across different parts of the world, and respond differently to therapy. How genetic and hormonal sex determinants impinge on cancer risk in concert with variations in human populations is a complex topic that requires a multifaceted approach at the interface of science and society.
Currently, most cancer research focuses on mechanisms of tumorigenesis to identify molecular targets for therapy rather than to prevent the disease. Measuring success in cancer prevention is difficult and funding agencies provide relatively limited support because the growing economic impact of preventing the disease is still poorly appreciated. To overcome these issues and to shift the research paradigm, it is essential to train a new generation of scientists aware of challenges and opportunities in cancer prevention and endowed with an interdisciplinary view on how to address them.
Cross-disciplinary educational efforts for doctoral and advanced master studies in cancer prevention are rare. To link research efforts in basic molecular and cellular biology with epidemiological and environmental studies, is key for decreasing risk of various cancer types and minimizing clinical problems resulting from under- or over-treatment of patients. Equally important is dissecting the role of epigenetic and genetic determinants of biological responses, such as sex hormones and chromosomes, for personalized efforts to detect and prevent malignant conversion of premalignant lesions and potentially cause their complete resolution.
In depth training and education are intimately linked with participation in cutting-edge research efforts. Research programs at CancerPrev are focusing on breast and skin cancer, as benchmarks of major clinical significance for primary, secondary and tertiary cancer prevention in organs with reproductive and non-reproductive functions, respectively. Other cancer types will be considered as CancerPrev further develops, such as colon, liver and prostate cancer.
Research results can take decades to translate into effective public health measures. In a rapidly developing world, it is essential to close the gap between basic and clinical researchers and operators in the public health and policy making sectors. Another activity of CancerPrev is hence to foster communication skills and outreach activity of participating members and their students with people with different backgrounds and the general public. This will be achieved through informational meetings, local workshops and discussions.
The following topics will be addressed as part of CancerPrev teaching, research and/or outreach activities, including, in addition, a personalized service for sex hormones measurements :
1) environmental pollutants and food products as endocrine disruptors
2) individual differences in levels and metabolism of endogenous steroid sex hormones (estrogens, progestogens, androgens)
3) exogenous modulation of sex hormones levels and activity (hormonal contraception, hormone replacement therapy and hormone ablation therapies, induction and maintenance of gender dysphorias)
4) interplay between sex hormone signaling and cancer stem cells, the tumor microenvironment and systemic factors such as the immune system and metabolism
5) modulation of sex hormones signalling plus/minus epigenome- and immune-targeting drugs as novel modalities of secondary and tertiary cancer prevention.
Gender and Sex : time to bridge the gap ?
The incidence of many cancer types arising in organs with non-reproductive functions is significantly higher in male than female populations, with associated differences in survival (Clocchiatti et al., 2016). Equally important, for secondary and tertiary cancer prevention, are the substantial differences in drug toxicity and response between the two sexes (Özdemir et al., 2018). Also, recent major advances in cancer immune therapy need to be put in the context of well known sex differences in the immune system (Özdemir and Dotto, 2019).
Together with occupational and/or behavioural factors, molecular differences between the two sexes, at cellular and organ/systemic levels, are likely to play a determining role. The focus of this program is on the combined impact that sexual hormones and sex chromosomes can have in this context on susceptibility to various cancer types and drug response.
The aim is to establish a multi-disciplinary forum for the generation of novel conceptual frameworks and approaches to these complex issues. Experts in human development and genetics, cancer cell biology, metabolism and immune system are being brought together with epidemiologists and clinical investigators to address the following topics:
- Genetics and epigenetics of sex determination
- Environmental impact
- Drug toxicology and pharmacological approaches (immunotherapy)
- Societal challenges and opportunities