Small molecules, big impact: advancing immune checkpoint inhibitors for cancer

Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors (ICIs) playing a pivotal role. However, current ICIs, primarily monoclonal antibodies, face significant challenges like poor tissue penetration, high production costs, and off-target effects. These limitations hinder their efficacy and accessibility. Due to these issues, there is an urgent need to explore alternative approaches. Small molecule drugs targeting immune checkpoints offer a promising solution, potentially overcoming these barriers and providing more effective cancer therapies.

A recent review (DOI: 10.20892/j.issn.2095-3941.2024.0034) by researchers from the University of Electronic Science and Technology of China, affiliated Sichuan Provincial People’s Hospital, published in Cancer Biology & Medicine on May 9, 2024, delves into the development of small molecule drugs targeting immune checkpoints. The study presents an innovative approach to cancer therapy by focusing on the efficacy and mechanisms of small molecule ICIs.

The study underscores the advantages of small molecule ICIs over traditional antibody-based therapies. These small molecule drugs exhibit superior tissue permeability, better oral bioavailability, and favorable pharmacokinetic properties. Key examples include BMS-202, which induces PD-L1 dimerization to block PD-1/PD-L1 interactions, and CA-170, the first oral ICI to enter clinical trials. Additionally, YPD-29B has shown promising results in promoting PD-L1 degradation and enhancing antitumor immunity. The research also highlights the potential of combining small molecule ICIs with other therapeutic strategies, such as immune regulation and anti-angiogenesis, to amplify treatment efficacy. This comprehensive analysis of various small molecule inhibitors demonstrates their potential to revolutionize cancer treatment by addressing the limitations of antibody-based ICIs and offering more effective and accessible options for patients.

Dr. Chuan Xu, the lead researcher, stated, “The development of small molecule ICIs represents a significant leap in cancer therapy. These drugs not only address the limitations of current antibody-based therapies but also offer new avenues for combination treatments, enhancing overall efficacy and patient outcomes.”

The study’s findings suggest that small molecule ICIs could revolutionize cancer treatment, providing more accessible and cost-effective options. By improving tissue penetration and reducing production costs, these drugs have the potential to make advanced cancer therapies more widely available. The research paves the way for further exploration and clinical trials, aiming to establish small molecule ICIs as a cornerstone of modern cancer treatment.

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References

DOI

10.20892/j.issn.2095-3941.2024.0034

Original Source URL

https://doi.org/10.20892/j.issn.2095-3941.2024.0034

Funding information

This study was supported by the National Natural Science Foundation of China (Grant Nos. 82203539 and 92259102), Provincial Cooperation Project of Science and Technology Department of Sichuan Province (Grant No. 2023YFSY0043), the National Key Research and Development Program of China (Grant No. 2023YFC3402100).

About Cancer Biology & Medicine 

Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 5.6, 5 year IF 5.9), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).