Targeting alternative splicing for cancer therapy using South African medicinal plants and phytocompounds

Cancer is one of the leading causes of death worldwide including South Africa. Chemotherapy remains the main method of cancer treatment. Despite advances in chemotherapy for the treatment of cancer, costs, side effects and development of resistance to chemotherapy are major obstacles particularly in the global south. Colorectal cancer (CRC), cervical cancer (CVC) and oesophageal cancer (EC) are ranked the third, fourth and eighth most common cancers worldwide, respectively. Colorectal cancer and EC have a global mortality rate of 5.8 and 5.3%, respectively. In South Africa, CRC is the fourth most common cancer, with a low survival rate of 8.1. Additionally, the highest rates of cervical cancer incidence and mortality are in low-and-middle income countries. Oesophageal cancer is responsible for the second highest number of cancer-related mortalities, and has a 5 year relative survival rate of 4% in metastatic disease. Motivated by this evidence and challenges we intend to investigate how South African medicinal plant extracts and phytocompounds that regulate alternative splicing can affect cancer growth and progression in these cancers.. It is estimated that more than 60% of anticancer drugs in clinical use originate from natural products, thereby pointing to their importance as promising sources for cancer drug development . Alternative splicing can contribute to all cancer hallmarks, and alternatively spliced isoforms expressed in cancer are fundamental for the development of tumour-specific molecular targets for prognosis and therapy. Several alternative splicing factors are overexpressed and highly mutated in different cancer tissues. Additionally, changes in the splicing patterns of various alternative splicing events were identified in tumours demonstrating a prominent role in carcinogenesis, and a potential prognostic indication. Developing new pharmaceuticals that target alternative splicing may create new therapeutic avenues for treating cancer.