Assessment of the evolution of cancer treatment therapies

Abstract

Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

Figure 1.

History of antibodies. In 1890 von Behring and Kitasato showed that it was possible to generate anti-toxins (against tetanous, diphtheria), and soon after, therapy with antiserum containing antitoxins were used in patients. It took several years to purify the antibodies (1926) and even more to know their structure. On 1975, Milstein and Köhler developed the first monoclonal antibody, and the generation and application of monoclonal antibodies started (on diagnosis, research and therapy), initiating the Modern Immunology. In the 1980s, the first anti-tumoral monoclonal antibody was tested and molecular biology techniques started to designed chimeric and humanized antibodies. Later on, transgenic mice carrying human Ig genes and other animal models were used to produce fully human antibodies.

Figure 2.

Several antibody molecules and some antibody fragments are shown. Chimeric (mouse-human) antibodies carry mouse heavy and light variable domains (in yellow) being the rest of the molecule of human origin (in red). In the case of humanized antibodies, only the hypervariable regions are mouse derived (in yellow). It is possible to generate bi-specific antibody molecules, using different heavy and light chains (each arm will have a different specificity). Fab: fragment antigen binding; scFv: single chain Fragment variable; Vh: variable domain from the heavy chain.

Figure 3.

A collection of scanning and transmission electron microscope images (color added) of different nanoscale or nanostructured materials used in biomedicine. (A) Silver nanowires; (B) gold nanoparticles; (C) SiO₂/Au core/shell nanoparticles (nanoshells); (D) gold nanorods; (E) dense silica nanoparticles; (F) gold nanoparticles on an inorganic support; (G) mesoporous silica; (H) Poly(lactic-co-glycolic acid) (PLGA) microparticles; (I) Fe₃O₄/SiO₂ core/shell nanoparticles; (J) ZnO nanoparticles; (K) TiO₂ nanotubes; (L) Fe₃O₄ nanoparticles.

Figure 4.

Temporal evolution in the number of scientific papers published involving nano-based applications developed to fight cancer in the last decade. Document types include articles, reviews, meeting abstracts, patents, editorials, letters and news. (Source: ISI Web of Knowledge © The Thomson Corporation. Date of search: December, 2010.)*2010 indexing was incomplete at the time of search.