The Cyprus Cancer Research Institute (CCRI) is pleased to announce that the Institute has awarded four research grants of €200,000 each, through its “Bridges in Cancer Research Excellence” funding call.
Funding was allocated on a competitive basis to support researchers and innovators to set up interdisciplinary cancer research among the three founding partners of the Institute (University of Cyprus, Bank of Cyprus Oncology Centre, Karaiskakio Foundation). The awarded projects, in random order, are:
| CANCER, ALLOSTATIC LOAD, AND REGULATION OF EMOTIONS: HOW STRESS AND EMOTION REGULATION IMPACT MENTAL AND PHYSICAL HEALTH OF BREAST AND TESTICULAR CANCER PATIENTS. |
| Acronym: CARE |
| Principal Investigator: Dr Maria Karekla – University of Cyprus |
| Collaborating institutions: University of Cyprus & Bank of Cyprus Oncology Centre |
| Award: €200,000 |
| Duration: 3 years |
| Abstract: Improvements in cancer diagnosis and treatment strategies have led to more people living with cancer and concomitant mild-to-severe stress due to cancer-related health concerns and changes in life and functionality. Chronic stress can have a detrimental impact on patients’ health, as well as cancer progression and treatment outcomes, due to an over-activation of physiological systems involved in the body’s stress responses. Based on previous literature, we hypothesize that cancer-associated stress has toxic effects on health in patients with poor ability to manage emotions in a flexible and adaptive way. The CARE project aims to examine a wide range of biological and psychological stress markers in breast and testicular cancer patients: how their levels change throughout the first year after cancer diagnosis and how these biomarkers interact with patients’ emotion regulation ability and psychological flexibility. We will study the impact of these markers on physical and mental health and on cancer progression and treatment response using biochemical, epigenetic and behavioural techniques. We will also assess how these stress-related changes can be managed using a modern, brief, easy and accessible eHome-care, self-delivered intervention, via momentary ecological assessment of emotions and health indices, to enhance emotion regulation skills, functionality and wellbeing. To this end, after baseline assessment of immune, neuroendocrine, stress biomarkers and tumour epigenetics, as well as emotional responding to an experimental emotion induction procedure, breast and testicular cancer patients will be assigned to a self-administered, eHome-care intervention or wait-list control groups. Effects of the intervention will be assessed on the same biomarkers in up to 9 months follow-ups. Findings from this project will provide reliable markers to predict at risk cancer patients that can benefit from psychological interventions, but also evidence for the ability of already existing interventions to reduce cancer-related stress and its effects on physical and mental health outcomes. |
| A TECHNOLOGICALLY INTEGRATED DIGITAL PLATFORM FOR PERSONALISED PREDICTIONS O F METASTATIC BRAIN TUMOUR DEVELOPMENT AND RESPONSE TO TREATMENT |
| Acronym: PROTEAS |
| Principal Investigator: Dr Vasileios Vavourakis – University of Cyprus |
| Collaborating institutions: University of Cyprus & Bank of Cyprus Oncology Centre |
| Award: €200,000 |
| Duration: 3 years |
| Abstract: Brain metastases, or secondary brain tumors, occur in 10% to 30% of adults with cancer. Treatment for people who developed brain cancer metastasis is often surgery, radiation therapy or both. Clinical evidence suggests however that stereotactic radio-surgery (SRS), or in combination with whole brain radiotherapy (WBRT), can offer improved cancer patient survival and decreased morbidity. Despite this, prediction of response to treatment on a patient-specific basis still remains elusive, while there are no reliable tools for clinical decision making in patients with brain metastases. This research project aims to address this challenge and offers a multidisciplinary approach that encompasses medicine and cancer biology, physics and engineering. In the clinical branch, retrospective and prospective clinical efforts will be focusing on brain cancer patient metastases, from histologically proven breast and lung primary tumors, with patients referred to for SRS or stereotactic fractionated radiotherapy (SFRT). On the technological branch, the project will innovate by developing and delivering a technologically integrated digital platform for predicting and assessing the efficacy of external beam radiation treatments (SRS, SFRT) in individual patients with brain metastases. To accomplish this, novel image processing and radiomics algorithms, as well as cutting-edge personalised in silico models of the brain mechano-biology will be developed and will be integrated into the digital platform. The proposed platform will be validated and assessed for its accuracy, reliability, repeatability and reproducibility against pertinent clinical evidence of the clinical studies of this project. |
| MECHANISTIC AND PROGNOSTIC IMPLICATIONS OF THE EPIGENETIC ACETYLTRANSFERASE NAA40 IN CANCER CHEMORESISTANCE |
| Acronym: ChemoresistNAT |
| Principal Investigator: Dr Antonis Kirmizis – University of Cyprus |
| Collaborating institutions: University of Cyprus & Bank of Cyprus Oncology Centre |
| Award: €200,000 |
| Duration: 3 years |
| Abstract: Histone modifying enzymes and their mediated protein modifications constitute one of the main epigenetic mechanisms through which the cell regulates gene expression. Misregulation of these epigenetic enzymes and consequential changes in gene expression can lead to the development of cancer but, importantly, can also provide cancer cells with the necessary adaptation to resist drug therapy, which today remains one of the major obstacles in curative cancer treatment. Therefore, understanding how histone modifying enzymes and their underlying molecular mechanisms operate within cancer cells could highlight new avenues for circumventing therapeutic resistance. Previous work from our group and others has implicated the abundant and evolutionarily conserved histone modifier N-alpha acetyltransferase 40 (NAA40) in carcinogenesis. Specifically, we reported that NAA40 contributes to cancer cell growth by regulating the expression of key cancer-associated genes and NAA40 depletion sensitizes cells to anti-cancer agents. Consistent with these findings, recent preliminary evidence in vitro and in xenograft models indicates that NAA40 confers chemotherapeutic drug resistance to cancer cells. Accordingly, the main objective of this project is to decipher the precise molecular role of NAA40 in chemoresistance and evaluate its efficacy to predict drug response. To achieve this objective, biologists at the University of Cyprus and medical oncologists at the Bank of Cyprus Oncology Centre will join efforts in order to employ a combination of state-of-the-art epigenomic, transcriptomic and molecular techniques using cell-based assays and tissue specimens obtained from cancer patients. The proposed project will provide significant new scientific knowledge that will serve as paradigm for other protein N-terminal acetyltransferases (NATs), unveil novel non-genetic mechanisms of drug resistance and, importantly, contribute to cancer research aiming to develop more informed therapeutic approaches that will ultimately improve outcomes for cancer patients. |
| ENHANCING ADOPTIVE T CELL THERAPY VIA T CELL COSTIMULATION |
| Acronym: ACT-Costimulation |
| Principal Investigator: Dr Pavlos Costeas – Karaiskakio Foundation |
| Collaborating institutions: Karaiskakio Foundation & University of Cyprus |
| Award: €200,000 |
| Duration: 3 years |
| Abstract: The ability to harness the immune system has revolutionized cancer therapeutics giving rise to a new group of treatments termed cancer immunotherapy (CI). CI includes adoptive T cell therapy (ACT) whereby autologous tumour specific T cells are isolated from the patient, expanded in vitro and re-infused back to the patient, the use of autologous but genetically engineered T cells for ACT, dendritic cell-based cancer vaccines and immune checkpoint blockade therapy. ACT showed great promise and success in treating B-cell malignancies. ACT in solid cancers showed initial promise in metastatic melanoma but then faced a number of pitfalls in other types of solid tumours related to the properties of the tumours and the tumour microenvironment. A major parameter controlling the response of transferred T cells is their status (proliferative capacity and anti-tumour cytotoxicity) at the end of the in vitro manipulation that could involve only in vitro expansion and/or genetic manipulation to introduce a chimeric antigen receptor. We hypothesize that harnessing specific T cell costimulatory pathways can enhance further T cell preparation in vitro, at the molecular and cellular level, that translates into a more efficacious ACT modelled using in cancer mouse models. We also hypothesize that our in vitro protocols can benefit further, with increased in vivo efficacy, from the normalization of the tumour microenvironment mediated via in vivo pharmacological manipulations. |