The CellCOM group is an internationally recognized research group with extensive expertise in the field of connexin-linked diseases. The group has identified a novel regulator of cellular senescence, connexin43 (Cx43), which is also involved in inflammation, tissue remodeling and progression of age-related diseases, as well as a modulator of dedifferentiation processes and epithelial-to-mesenchymal transition. We have recently received the “Francisco Guitián Ojea” Award from the Galician Royal Academy of Sciences (RAGC) for our research in oncology (PCT/ES2020/070269, patent under licensing).
Our group discovered that chondrocytes in articular cartilage are connected by long cytoplasmic projections and cell-to-cell communication occurs via gap junctions formed by Cx43. We have also demonstrated that the overactivity of Cx43 since early stages of the disease is involved in osteoarthritis (OA) progression, finding a new therapeutic target for the treatment of OA. These results have been recognized by the Spanish Society of Rheumatology (SER) with two awards in two different panels; Basic Science and Osteoarthritis and with one award in the congress of the international gap junction community (IGJC Canada 2019). In line with these results, our group has registered two international patents with innovative therapeutic strategies based on the use of lectins and peptidomimetics to target Cx43 for the treatment of OA (PCT/US2014/045229; PCT/EP2020/071242).
New strategies to increase the efficacy of immunotherapy and targeted therapies in metastatic cancer.
CellCOM group is now exploring the role of connexins and pannexins in metastasis and drug resistance. To do so, we are studying connexin/pannexin signalling pathways and cell-to-cell communication (hemichannels and gap junctions) within the tumour microenvironment to increase the efficacy of immunotherapy and targeted therapies currently in use in the clinic, such as BRAF/MEK inhibitors, CDK4/6 or PARP inhibitors.
Our group has recently found that modulation of a new target (mRNA and protein) through an innovative method involving exosome-based delivery systems, increases the efficacy and overcomes drug resistance in BRAF-mutated tumours (EU Patent: PCT/EP2021/077487; 1 manuscript under preparation), in line with ongoing promising research about the key role of connexins in resistance to CDK4/6 inhibitors in breast cancer and PARP inhibitors in advanced breast and ovarian cancer models (EP21382657 and EP22382009, respectively). Our group is also exploring the immunomodulatory activity of connexins which participates in the immunological synapses. We have started to explore the interaction between natural killer cells, (NKs) dendritic cells (DCs) and tumour cells to enhance the immune response to cancer and to improve tumour response to immunotherapies.
These research lines aim to explore innovative therapeutic strategies to improve the efficacy of cancer immune checkpoint inhibitors and targeted therapies where connexins play a dual role. All in all, the final goal is to increase the overall survival in metastatic cancer patients