Cancer Research and Personalised Medicine
11:25 - 13:05 | Lecture Room 201 (Level 2)
Chair: Prof. Pierre Schembri Wismayer
Ms Nadine Sciortino
Centre for Molecular Medicine and Biobanking
Ewing Sarcoma (EWS) is a rare but aggressive malignancy, accounting for 3% of paediatric cancers, predominantly affecting children and adolescents. Approximately 20–30% of cases occur within the first decade of life, with a median age at diagnosis of 15 years. EWS is driven by a characteristic chromosomal translocation producing the EWSR1-FLI1 fusion gene. Despite intensive multimodal treatment, survival outcomes, particularly in metastatic or relapsed cases, have plateaued, and treatment-related morbidity remains significant. In Malta, 18 cases were recorded between 2007 and 2022, with a potential increase in recent years.
This study evaluated the cytotoxic and differentiation-inducing potential of selected compounds in the SK-ES-1 EWS cell line to identify alternative or adjunct therapeutic strategies. Cell viability assays identified three polyphenols with significant antiproliferative effects. Polyphenol A induced dose- and time-dependent cytostatic effects at ≥15µM (p<0.01) and cytotoxic effects at higher concentrations (20–50µM, p<0.01–0.001), with flow cytometry confirming G0/G1 cell-cycle arrest and a progressive shift toward a sub-G0 population. Polyphenol B exhibited cytostatic effects at 3µg/mL (p<0.05–0.001) and cytotoxicity at 4.5–6µg/mL (p<0.001), with an increased sub-G0 population at higher concentrations. Polyphenol C showed strong cytotoxicity at 3–5µg/mL (p<0.05–0.001), arresting cells in G0/G1, while suppressing the G2/M population.
Compound D, a non-phenolic PKA activator, demonstrated differentiation-associated activity, as indicated by increased acetylcholinesterase activity (p<0.001) and neuron-like morphology, but induced dose- and time-dependent cytotoxicity with prolonged exposure. Sequential treatment studies revealed synergistic effects, with Compound D pre-treatment sensitising SK-ES-1 cells to Polyphenol A-induced cytotoxicity at sub-cytotoxic concentrations (p<0.001).
Future work will assess selectivity in non-cancerous cells and employ RNA sequencing with qPCR validation to elucidate underlying molecular mechanisms.
Ms Kimberly Fenech
Centre for Molecular Medicine and Biobanking
Human exposure to pesticides has been associated with cancer. Glyphosate, a widely used herbicide, is ubiquitous in food and human samples. Although colorectal cancer (CRC) is strongly influenced by diet, the molecular effects of glyphosate exposure on colon cells remain poorly understood. While regulatory authorities do not classify glyphosate as carcinogenic, emerging evidence of increased tumour incidence following exposure underscores the need for mechanistic studies. Here, we examined the effects of 5 µM of glyphosate (concentration pre-determined from cell viability assays and residue levels in food) for two weeks on four cell lines, three CRC (HCT116, LoVo, DLD1) (n=2) and one normal (CCD841) (n=2), using proteome profiling by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). Glyphosate-induced cell line specific molecular responses (p<0.05 from functional enrichment analysis). In CCD841, glyphosate affected extracellular matrix organisation, growth factor mediated signalling, and metabolism, suggesting early adaptive remodelling of cell matrix interactions and signalling homeostasis rather than oncogenic transformation. In HCT116, glyphosate upregulated glutamine and kynurenine metabolism to support cell survival. Several upregulated proteins in DLD1 following exposure were enzymes involved in glycoprotein and proteoglycan modifications known to regulate cell proliferation, migration, and invasion. In LoVo, glyphosate triggered strong metabolic activation, increasing glycolysis, fatty acid uptake and oxidation, lysosomal glycogen breakdown, and altered NADH/NADPH production, promoting survival, migration, and invasion. Additional altered pathways (p<0.05) in all the cells included the cell cycle, nucleotide metabolism (with implications for chemoresistance), chromatin remodelling, and oxidative stress. Ongoing work aims to define the consequences of these molecular alterations.
Dr Olaf Woods
Centre for Molecular Medicine and Biobanking
The PACT-V project and related research aim to produce an individual tumour vaccine from each patient's tumour, starting by working with companion animals, particularly dogs. The PACT-V project is funded by the Cancer Research and Innovation Hub Malta, through Xjenza Malta. In collaboration with Happy Paws veterinary clinic and Metallform Ltd., the CATSCI lab team is developing a personalised tumour tissue-derived vaccine, building on previous research by Ohno (available to human patients at the Ikiru Clinic in Germany). As doctoral students, we are using an in vivo model with the metastatic mouse breast cancer cell line 4T1 to study this common cancer and its response to the immunotherapies being developed by modifying and improving on the Ohno methodology.
Breast cancer cells are fixed in formalin and then further processed in a proprietary method into a vaccine, which is then used as a therapeutic to treat the cancer. Since the cell line is tagged with a red fluorescent protein, we can follow the spread of the disease and its response to therapy. We are also studying the biochemical nature of the modifications we are producing in the tumour tissue-derived vaccine to understand its mechanism of action. Previous work has already shown significant and curative effects in rats and in dogs.
With Happy Paws, we plan to use an optimised version of this therapy to treat dogs with cancer which is inoperable and with Metallform Ltd., we are developing a device which should allow the self-contained development of a tumour biopsy into the vaccine, without the need for Good Manufacturing Practice (GMP) labs, such that if it works, it can eventually be adapted to human tumours.
Ms Abigail Anne Dalli
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery
Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase that functions as a tumour suppressor through regulation of key signalling pathways involved in cell survival and proliferation, including mTOR, Wnt and MAPK. PP2A is a heterotrimeric protein composed of a scaffold (PP2Aa), a regulatory (PP2Ab) and a catalytic subunit (PP2Ac), each of which exists in multiple isoforms. Dysregulation of PP2A activity is frequently observed in cancer, yet the functional significance of several emerging PP2A isoforms, particularly those of the catalytic subunit, remains poorly understood.
Previous work by Professor Godfrey Grech’s research team identified two novel PP2Ac isoforms in chronic myeloid leukaemia resulting from exon deletion events: PP2Ac Δ2 and PP2Ac Δ5. The primary objective of this PhD project is to characterise the PP2Ac isoform landscape across different cancer cell types and assess the potential of these isoforms as diagnostic or prognostic biomarkers. These isoforms have been detected at the RNA level in colorectal and breast cancer cell lines, and a third novel isoform lacking exon 3 (PP2Ac Δ3) has been identified at high levels in the triple-negative breast cancer cell line MDA-MB-231.
The abundance of PP2Ac isoforms is being analysed using bulk RNA sequencing, isoform-specific RNA sequencing, and RT-qPCR, alongside protein-level detection by western blotting. Comparative analyses are being performed in both 2D and 3D cell culture models. In parallel, PP2Ac wild-type and isoform clones have been generated using Sequence- and Ligation-Independent Cloning. Recombinant expression, stability and purification strategies are being optimised in E. coli and Pichia pastoris. Finally, molecular dynamics simulations are being employed to investigate the structural stability and conformational dynamics of PP2A isoform complexes, providing mechanistic insights not accessible through experimental approaches alone.
Ms Claire Caruana
Department of Nursing, Faculty of Health Sciences
Background: Despite international guidelines, patients with haematological malignancies receiving systemic anticancer treatment (SACT) often face significant unmet supportive care needs (SCNs). The nature of the malignancy and associated SACT protocols creates an ‘ecological disaster’ affecting both the patient and their informal caregiver.
Aim: To explore and map the supportive care needs (SCNs) of persons diagnosed with haematological malignancies receiving SACT and their caregivers to inform the development of a responsive, evidence-based supportive care pathway.
Methods: Guided by a pragmatic philosophical paradigm and Fitch’s (2008) Supportive Care Framework, this study utilises an action research (AR) strategy. Phase 1 employed a convergent mixed-methods design:
Findings: Preliminary quantitative data confirmed the validity of the Maltese SCNS tools (Cronbach’s alpha >0.70). Qualitative findings revealed a ‘clinical fortress’ where medical care is prioritised over psychosocial stressors. Key themes included the ‘emotional abyss’ and the ‘family ripple effect,’ highlighting systemic barriers and a disconnect between current services and actual requirements.
Conclusion: Findings emphasise the need to transition from a purely medical model to an integrated, person-centred pathway. These results provide the empirical foundation for a local supportive care pathway tailored to the unique haematological trajectory.