Novel mechanisms and approaches in the medical therapy of solid cancers.

Major advances in cancer research in the last two decades have provided us with a better understanding of the dynamics of the cancer cell and its microenvironment. This has consequently led to the development of new therapies and treatment strategies either targeting the cancer cell or the tumor microenvironment. In this review we will discuss the major existing and promising future treatment approaches in medical oncology. Therapies targeting the cancer cell include hormonal therapies, small molecules, and monoclonal antibodies. They are used mostly in the advanced disease setting. Strategies developed more recently are antibody drug conjugates (trastuzumab emtansine and radioimmunotherapy) and oncolytic viruses. Molecular therapies targeting the tumor microenvironment include angiogenesis inhibitors and the new agents and approaches that interfere with the immune system (immune checkpoint inhibitors and adoptive cell therapy). The development of resistance (primary and acquired) to targeted therapies is unfortunately a common phenomenon that can be overcome or delayed using multiple strategies like the use of second- or third-generation molecular therapies targeting the emerging resistant mutations or genetic abnormalities, multitargeted drugs, and drug combinations targeting the same or different proteins, and/or the use of modern immunotherapy. Molecular targeted therapies have a distinct array of side effects that can be mechanism-based, but can also be unpredictable. Although the progress in research brings a vast amount of new information about cancer and its environment, it renders the field of oncologic research more and more complex with fragmentation of tumor entities. These are important challenges for future research and precision oncology.