The road to precision cancer therapy - history and strategies

Abstract

Human cancer has been recognized for thousands of years as a leading cause of death with complex pathophysiology and remains as the most challenging disease to achieve curative therapy. Selecting the right treatment for cancer patients based on molecular diagnostics continues to evolve. Recent explosion in the knowledge of molecular genetics, epigenomics, cellular biology and immunology of cancer has influenced the development of targeted therapies for specific tumour types as well as for the individual patients. Chemotherapy has remained as the backbone of cancer therapy, but limited response rates, side effects and resistance have increasingly shifted the focus on approaches to harness targeted therapy directed to specific molecular alterations at the intracellular genomic and epigenomic levels and the microenvironment which includes extracellular regulatory molecules and surrounding cells. Immunotherapies are designed to interfere with the immune escape mechanisms of cancer cells such as negative immunologic regulators (checkpoints) and/or by stimulating the patient’s adaptive immune system against specific tumour antigens. Inherent complexity and heterogeneity oftumours as depicted by the multi-modular molecular network (MMMN) cancer progression model suggest that most cancers may not be treatable with just monotherapy and would require a combination of therapies, both traditional and targeted therapies as well as immunotherapies to lengthen the patients’ life. The availability of novel technologies and generation of large-scale oncology data from multiple sources of analysis including genomics has created a promising environment for revolutionizing cancer diagnosis, drug discovery, treatment and prevention. Advanced computational algorithms are currently being developed for automatically interpreting input data to assist inter-professional teams to provide calibrated recommendations with minimal toxicities to help the physicians to make effective therapeutic decisions.