Improvement of Cancer Immunotherapy by Combining Molecular Targeted Therapy | Frontiers in Tumor Immunity

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Concluding Remarks

As discussed in this article, altered activation of various oncogenes and signaling in both cancer cells and immune cells can be an attractive target to reverse immunosuppressive conditions in tumor-associated microenvironments of cancer patients. Signal inhibitors may augment current cancer immunotherapy, in addition to its possible direct anti-tumor effects through inhibition of cancer cell proliferation and invasion. However, its total in vivo activity should be carefully evaluated because it may also cause various adverse effects, including possible inhibition of anti-tumor immune responses. In this regard, mutated-molecule-specific inhibition such as that of the mutant BRAF-selective inhibitors is one of the promising strategies. Activation of STAT3 appears to shift immune response toward cancer’s advantage, thus, its inhibition is attractive for possible improvement of anti-tumor immune responses. Altogether, combination therapy using molecular targeted drugs and various immunotherapies such as cancer vaccines and check point blockade is a promising strategy to treat cancer patients. Future clinical trials may demonstrate the proof of concept of this strategy.

However, there are several obstacles to overcome before the benefits of combination therapy can reach the patients. One such obstacle is scientific. Although quite a few signal inhibitors, immunotherapies, and combined therapies have shown promising results in experimental settings, mouse model, and human are different. A successful treatment in mouse models may not work in patients. Therefore, for the selection of appropriate molecular targets and inhibition methods, further understanding of human cancer immunopathology is deeply essential and urgently desired. Another obstacle is a pragmatic one, which may arise when individual therapies in a combination therapy are developed and/or owned by different companies. The issues of company regulations, patents, and logistics could become a barrier between research and clinical translation. The core idea of combination therapy is that by using multiple already-available therapies, cancer patients are able to gain greater-than-sum benefits. Therefore, it is crucial that institutions and companies to look beyond self-interests and work together to reach a common goal. Academic institution may mediate the cooperation between companies and provided combination therapies to patients.