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Published on: January 19, 2019
Combining cancer immunotherapy and targeted therapy
1Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, United States. aribas@mednet.ucla.edu
Abstract:
The ability to pharmacologically modulate key signaling pathways that drive tumor growth and progression, but do not negatively impact the function of lymphocytes, provides avenues for rational combinatorial approaches to improve the antitumor activity of tumor immunotherapies. Novel targeted agents can very specifically block oncogenic events in cancer cells, leading to a pro-apoptotic milieu and a potential increase in sensitivity to recognition and attack by cytotoxic T lymphocytes (CTLs). Furthermore, targeted pathway modulation in lymphocytes may change their function and have activating effects in some instances. When tested together with recently developed powerful tumor immunotherapies, such combinations may exploit the highly specific targeting of oncogenes with small molecule inhibitors to lead to high frequency of tumor regressions, and merge this benefit with the durable responses achievable with effective tumor immunotherapies.
Insights
Targeted therapies can enhance cancer immunotherapy by blocking tumor growth pathways without harming immune cells. Combining these agents with immunotherapies may improve tumor regression and durable responses.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Tumor growth and progression are driven by specific signaling pathways.
- Current tumor immunotherapies show promise but can be enhanced for greater efficacy.
- Targeting oncogenic pathways offers a strategy to improve antitumor responses.
Purpose of the Study:
- To explore the potential of pharmacologically modulating tumor-driving signaling pathways.
- To investigate combinatorial approaches combining targeted agents with tumor immunotherapies.
- To assess the impact on lymphocyte function and antitumor activity.
Main Methods:
- Utilizing novel targeted agents to specifically block oncogenic events in cancer cells.
- Modulating key signaling pathways in both cancer cells and lymphocytes.
- Evaluating the combined effects of targeted agents and tumor immunotherapies.
Main Results:
- Targeted agents can induce a pro-apoptotic environment in cancer cells.
- This may increase cancer cell sensitivity to cytotoxic T lymphocytes (CTLs).
- Pathway modulation in lymphocytes might yield activating effects, enhancing antitumor immunity.
Conclusions:
- Combinatorial strategies merging targeted therapy and immunotherapy can improve tumor regression frequency.
- This approach aims to combine the specificity of small molecule inhibitors with the durability of immunotherapy.
- Pharmacological modulation offers a rational design for enhanced cancer treatment.
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