Combination of targeted therapy and immunotherapy in melanoma |
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Authors: | Christian U Blank Anna I Hooijkaas John B Haanen Ton N Schumacher |
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Institution: | (1) Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Ziekenhuis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;(2) Division of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Ziekenhuis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands |
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Abstract: | The treatment of human melanoma has progressed markedly in recent years. Building on the observation that immune recognition
is a frequent event in melanoma, a series of immunotherapeutic approaches have been evaluated in clinical trials, culminating
in the first phase III study improving overall survival of melanoma patients since 20 years. However, the response rates seen
upon immunotherapeutic interventions such as anti-CTLA4 treatment are often low. Furthermore, clinical responses can take
several weeks to develop, during which time stage IV melanoma patients often deteriorate. Recent advances in our understanding
of the genetic lesions in human melanoma now also allow the specific targeting of the signaling pathway alterations in this
disease. Such targeted therapies can lead to high response rates, although the duration of these responses is thus far relatively
short. We suggest that the combination of immuno and targeted therapy offers potential for synergy for both conceptual and
practical reasons. In this review, we will discuss the potential and possible limitations for such combination therapy, and
we describe the most promising combinations of targeted therapy and immunotherapy that can be tested in the clinic in the
coming years. The concept of induction therapy by small molecule administration and consolidation by immunotherapeutics also
has potential for the treatment of other human cancers. |
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