Non-Communicable Diseases

Cancer

Four Groups in Trieste, one in Cape Town, and one in New Delhi investigate the genetic and molecular mechanisms of cancer development. In Cape Town, the Cancer Genomics Group (Zerbini) develops novel therapeutics targeting various cellular proteins that are deregulated in cancer. The Protein Networks Group in Trieste (Myers) uses high-throughput mass spectrometry to perform proteomics studies to understand how protein complexes regulate normal and cancer cell behaviour, particularly in the process of protein modification. The Molecular Hematology Group in Trieste (Efremov) is interested in deciphering the intracellular signaling pathways that control the proliferation, differentiation and survival of normal and malignant B-lymphocytes. A particular focus is the study, in both patients’ cells and animal models, of the mechanisms leading to the development of chronic lymphocytic leukemia (CLL). The Membrane Protein Biology Group in Delhi (Arulandu) strives to uncover the molecular mechanisms underlying the function of membrane proteins, focusing on chloride intracellular channels as potential novel anti-cancer targets. The Tumour Virology Group in Trieste (Banks) investigates the mechanisms by which Human Papillomaviruses (HPVs) infect cells and ultimately cause cervical cancer.

Highlights 

The Cancer Group in Cape Town is making great strides in identifying The Hematology Group in Trieste made major advances in understanding the development of Diffuse Large B Cell Lymphomas (DLBCL) (Sasi et al., 2019 Leukhemia 33; 2416-2428). In this study they found that 50% of DLBCLs have downregulated SHP1, which results in the constitutive activation of the B cell receptorpathway. Thisactivationresultsintheresistanceofthesetumorstothechemotherapeuticagent venetoclax. Importantly, the Group demonstrated that targeting the activated BCR pathway with other inhibitors sensitizes these tumors to venetoclax. The Tumour Virology Laboratory identified how blocking phosphorylation of the Human Papillomavirus (HPV) E7 oncoprotein offers an exciting prospect for novel forms of therapeutic intervention in cervical cancer and other HPV associated malignancies. (Basukala et al., 2019 PLoS Path). Inhibiting phosphorylation of E7 reduces cell proliferation and, most importantly, blocks invasive potential, suggesting that therapies targeting the kinase which phosphorylates E7 would reduce tumour invasion. The Cancer Genomics Group have explored the involvement and relevance of Axl in cancer in order to test its efficacy as a therapeutic target. The Group identified one compound (Paccez JP et al.. Oncogenesis 8:14. 2019) having effects in tumor cell proliferation with no effect in normal cells with specificity for the Axl protein. This compound revealed to be safe and showed a synergistic effect with chemotherapeutic agents that current employed in the clinic and represents a new entry point for treatment.