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Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer
Paul E Hughes1, Sean Caenepeel1, Lawren C Wu2
1Department of Oncology, Amgen, Inc, Thousand Oaks, CA, USA.
Abstract:
Many advances in the treatment of cancer have been driven by the development of targeted therapies that inhibit oncogenic signaling pathways and tumor-associated angiogenesis, as well as by the recent development of therapies that activate a patient's immune system to unleash antitumor immunity. Some targeted therapies can have effects on host immune responses, in addition to their effects on tumor biology. These immune-modulating effects, such as increasing tumor antigenicity or promoting intratumoral T cell infiltration, provide a rationale for combining these targeted therapies with immunotherapies. Here, we discuss the immune-modulating effects of targeted therapies against the MAPK and VEGF signaling pathways, and how they may synergize with immunomodulatory antibodies that target PD1/PDL1 and CTLA4. We critically examine the rationale in support of these combinations in light of the current understanding of the underlying mechanisms of action of these therapies. We also discuss the available preclinical and clinical data for these combination approaches and their implications regarding mechanisms of action. Insights from these studies provide a framework for considering additional combinations of targeted therapies and immunotherapies for the treatment of cancer.
Insights
Targeted cancer therapies, like those inhibiting MAPK and VEGF pathways, can enhance immune responses. Combining these with immunotherapies targeting PD1/PDL1 and CTLA4 shows promise for improved cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Cancer treatment advances include targeted therapies and immunotherapies.
- Targeted therapies can modulate host immune responses, impacting tumor biology.
- Immune-modulating effects of targeted therapies support combination with immunotherapies.
Purpose of the Study:
- To discuss immune-modulating effects of targeted therapies against MAPK and VEGF pathways.
- To explore synergistic potential of these targeted therapies with PD1/PDL1 and CTLA4 immunotherapies.
- To examine rationale, mechanisms, and data for these combination approaches.
Main Methods:
- Review of immune-modulating effects of targeted therapies (MAPK, VEGF).
- Analysis of synergy with immunomodulatory antibodies (PD1/PDL1, CTLA4).
- Critical examination of preclinical and clinical data for combination strategies.
Main Results:
- Targeted therapies can increase tumor antigenicity and T cell infiltration.
- These effects provide a rationale for combining targeted therapies with immunotherapies.
- Preclinical and clinical data support the investigation of these combinations.
Conclusions:
- Targeted therapies against MAPK and VEGF pathways exhibit immune-modulating effects.
- Combining targeted therapies with immunotherapies (anti-PD1/PDL1, anti-CTLA4) is a promising strategy.
- Insights guide future combinations of targeted therapies and immunotherapies for cancer treatment.
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