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Focus on PD-1/PD-L1-Targeting Antibodies in Colorectal Cancer: Are There Options Beyond Dostarlimab, Nivolumab, and
Mateusz Kciuk1, Katarzyna Wanke1, Weronika Kruczkowska1,2
1Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.
Abstract:
The PD-1/PD-L1 pathway has emerged as a critical target in colorectal cancer (CRC) immunotherapy, with pembrolizumab, nivolumab, and dostarlimab demonstrating significant clinical efficacy, particularly in microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) tumors. However, a growing number of additional PD-1/PD-L1 inhibitors, including AMP-224, atezolizumab, avelumab, camrelizumab, durvalumab, envafolimab, sintilimab, spartalizumab, tislelizumab, and toripalimab, are currently under investigation, offering new possibilities for the expansion of treatment options. This review evaluates the therapeutic potential of these emerging agents, assessing their clinical development, mechanisms of action, and potential advantages over established therapies. Additionally, it explores key challenges such as primary and acquired resistance, limited efficacy in microsatellite-stable (MSS) CRC, and the complexities of combination strategies aimed at enhancing immunotherapeutic responses. By addressing these obstacles and highlighting prospects, this review provides insights into the evolving landscape of PD-1/PD-L1-targeted therapies in CRC and their potential to improve patient outcomes.
Insights
New PD-1/PD-L1 inhibitors show promise for colorectal cancer (CRC) immunotherapy, especially for MSI-H/dMMR tumors. This review explores emerging agents, challenges like resistance, and combination strategies to improve patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- The PD-1/PD-L1 pathway is a key target in colorectal cancer (CRC) immunotherapy.
- Established agents like pembrolizumab, nivolumab, and dostarlimab show efficacy in MSI-H/dMMR CRC.
- Numerous novel PD-1/PD-L1 inhibitors are under investigation.
Purpose of the Study:
- To evaluate the therapeutic potential of emerging PD-1/PD-L1 inhibitors in CRC.
- To assess their clinical development, mechanisms of action, and advantages over existing therapies.
- To explore challenges and prospects in PD-1/PD-L1-targeted CRC treatment.
Main Methods:
- Review of clinical development and mechanisms of action of novel PD-1/PD-L1 inhibitors.
- Assessment of efficacy in different CRC subtypes (MSI-H/dMMR vs. MSS).
- Exploration of challenges including resistance and combination strategies.
Main Results:
- Emerging PD-1/PD-L1 inhibitors offer expanded treatment possibilities for CRC.
- Significant challenges remain, including primary and acquired resistance, particularly in MSS CRC.
- Combination strategies are being explored to enhance immunotherapeutic responses.
Conclusions:
- The landscape of PD-1/PD-L1-targeted therapies in CRC is rapidly evolving.
- Emerging agents hold potential to improve outcomes, but resistance and MSS CRC require further attention.
- Continued research into novel agents and combination therapies is crucial for advancing CRC immunotherapy.
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