The incidence of cancer is rising in parallel with an ageing populous thus increasing the strain on both treatment options and budgets for healthcare providers worldwide. New cancer therapies are being developed but at what cost? The new treatments are expensive and poor survival rates still exist for some cancers. What is needed now is to prevent or at least limit the disease occurring in the first place. This review evaluates the current situation and the progress in upcoming strategies as well as suggesting some areas for further research within the increasingly important field of cancer chemoprevention. The key principles of cancer chemoprevention are discussed and areas for improvement highlighted. Despite significant progress, chemoprevention has not been widely adopted. Cancer chemoprevention has many challenges to face but this only emphasises the size of the task. These hurdles include a lack of awareness of the benefits, a lack of interest and a lack of investment in taking prevention forward. Despite the huge potential importance of cancer prevention and clinical success stories such as the well-publicised HPV vaccine, the challenges remain significant. With cancer and its treatment being a global issue, the opportunities offered by chemoprevention must be re-evaluated and uptake of chemoprevention actively encouraged. If chemoprevention is to be adopted successfully, a holistic approach is required. This approach will involve multidisciplinary teams of healthcare providers and scientists with the big challenge particularly for medicinal chemists being to design and synthesise the ideal chemopreventative agent.

Despite continued efforts, there remain no disease-modifying drugs approved by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) to combat the global epidemic of Alzheimer’s disease. Currently approved medicines are unable to delay disease progression and are limited to symptomatic treatment. It is well established that the pathophysiology of this disease remains clinically silent for decades prior to symptomatic clinical decline. Identifying those at risk of disease progression could allow for effective treatment whilst the therapeutic window remains open for preservation of quality of life. This review aims to evaluate critically the current advances in the interpretation of tau-based biomarkers and their use to provide insights into the onset and progression of Alzheimer’s disease, whilst highlighting important future directions for the field. This review emphasises the need for a more comprehensive analysis and interrogation of tau within biological fluids, to aid in obtaining a disease specific molecular signature for each stage of Alzheimer’s disease. Success in achieving this could provide essential utility for presymptomatic patient selection for clinical trials, monitoring disease progression, and evaluating disease modifying therapies.

Objectives: With the development of new technologies capable of detecting low concentrations of Alzheimer’s disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of AD is nearing reality. This study aims to consider the evidence of total and phosphorylated tau as blood-based biomarkers for mild cognitive impairment (MCI) and AD when compared to healthy controls. Methods: Studies published between 1 January 2012 and 1 May 2021 (Embase and MEDLINE databases) measuring plasma/serum levels of tau in AD, MCI, and control cohorts were screened for eligibility, including quality and bias assessment via a modified QUADAS. The meta-analyses comprised 48 studies assessing total tau (t-tau), tau phosphorylated at threonine 181 (p-tau181), and tau phosphorylated at threonine 217 (p-tau217), comparing the ratio of biomarker concentrations in MCI, AD, and cognitively unimpaired (CU) controls. Results: Plasma/serum p-tau181 (mean effect size, 95% CI, 2.02 (1.76–2.27)) and t-tau (mean effect size, 95% CI, 1.77 (1.49–2.04)) were elevated in AD study participants compared to controls. Plasma/serum p-tau181 (mean effect size, 95% CI, 1.34 (1.20–1.49)) and t-tau (mean effect size, 95% CI, 1.47 (1.26–1.67)) were also elevated with moderate effect size in MCI study participants compared to controls. p-tau217 was also assessed, albeit in a small number of eligible studies, for AD vs. CU (mean effect size, 95% CI, 1.89 (1.86–1.92)) and for MCI vs. CU groups (mean effect size, 95% CI, 4.16 (3.61–4.71)). Conclusions: This paper highlights the growing evidence that blood-based tau biomarkers have early diagnostic utility for Alzheimer’s disease. Registration: PROSPERO No. CRD42020209482.