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Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...

Enzyme immunoassays showed significantly elevated content of matrix metalloproteinase 7 and type 1 tissue inhibitor of metalloproteinases in tumors compared to adjacent histologically unchanged mucosa of patients with colorectal cancer; the levels of metalloproteinase 9 and type 4 tissue inhibitor of metalloproteinases were virtually the same in the tumors and mucosa. Plasma concentrations of the studied proteins did not correlate with their levels in the tumor, did not surpass the normal, and did not decease after removal of the primary tumor in the majority of patients.

The content of activated (phosphorylated) form of proteinkinase B in tumors and homologous tissues of 46 patients with breast cancer was measured by enzyme immunoassay. Activity of proteinkinase B was increased in tumors of 48% patients in comparison with homologous histologically unchanged tissue. Activity of proteinkinase B in hormone-dependent mammary tumors was significantly higher than in tumor tissue from patients with negative receptor status.

Cancer screening literature was discussed in this review publication. Broad spectrum of studies was used to make conclusion about effectiveness of screening methods in reaching its major objectives, perspective of screening methods for several cancer types were also discussed. Qualitative assessment of studies was done. Cervical cancer, breast cancer and colorectal cancer screening was proved to be effective. Effectiveness of prostate and lung cancer screening as well as population-based stomach cancer prevention is also discussed. Negative and inconclusive results of screening studies of the other cancer types were also mentioned and perspectives for future diagnostics option for cancer screening were given.