IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER

J Pharm Pharmacogn Res 2(Suppl. 1): S1, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture

PL 002: IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER

Lage Dávila A.

Director General, Centro de Inmunología Molecular, Cuba.
Abstract

Age-adjusted cancer mortality rates are showing a slow, but clear trend to decline in some countries. However, such decline is mostly due to reduction in tobacco smoking and to earlier diagnosis of some tumors. Long term control of advanced cancer continue to be a goal very hard to attain: Survival gains over the last three decades for many tumors are measured in months, not years. Four major barriers prevent a faster progress: the complexity of networks for the control of cell proliferation; the heterogeneity of cancer cells; the mutation rate; and our genome-environment mismatch. They challenge the classic pharmacology paradigm of “one molecular target/one specific drug¨. Targeted therapy, the most recent acquisition for the treatment of advanced cancer, together with its impressive short term effects,
illustrate the limitation of the strategy, due to the fast appearance of resistance. The complexity of regulatory networks will demand simultaneous intervention on several molecular targets and capacity to handle the ¨dual effects¨. Patient to patient heterogeneity and cell to cell heterogeneity will demand personalized medicine and clinical trials in smaller patient niches. Mutation rates will need the mobilization of biologic mechanisms, such as the immune system, which could evolve together with the tumor. Finally these mechanisms should act in a genetic background which has not been selected by evolution for protecting health in the post-reproductive period of human life. Neither classic screening strategies of pharmacology, nor the current regulatory context for drug development are well suited for facing these challenges. Biotechnology drugs offer the possibility of innovative approaches. Recent evidences related to the effect of monoclonal antibodies and therapeutic vaccines, and data related to the control of the immune response, epitope spreading, pathways of apoptosis, oncogene addiction and immuno-senescence point out the possibility to stepwise transform the clinical course of advanced cancer into that of a chronic disease compatible of years of quality life.