Translating CD47-targeted therapy in gastrointestinal cancers - Insights from preclinical to clinical studies

Sep 21, 2026

Review examining the role of CD47 in gastrointestinal cancers, using an in-depth survey of more than 100 preclinical and clinical studies on CD47 inhibition. The analysis explains how CD47 blockade may enhance existing treatment efficacy by strengthening immune responses against cancer cells while addressing the need to balance toxicity and therapeutic performance through improved CD47 inhibitors. It highlights rationale for combining CD47 antibodies with chemotherapy, radiotherapy, or other targeted therapies to improve outcomes, and calls for continued research to refine translation into clinical treatment plans.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

SUMMARY

INTRODUCTION

CD47 AND THE TUMOR MICROENVIRONMENT OF GASTROINTESTINAL CANCERS

CD47 and SIRPa in immune regulation

iScience ll OPEN ACCESS Review Translating CD47-targeted therapy in gastrointestinal cancers: Insights from preclinical to clinical studies Changgan Chen,1 Fengchun Lu,1 Heguang Huang,1,* and Yu Pan (潘誉)1,2,* 1Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou 350001, People’s Republic of China 2The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China *Correspondence: [heguanghuang22@163.com](heguanghuang22@163.com) (H.H.), [yupan199002@163.com](yupan199002@163.com) (Y.P.) [https://doi.org/10.1016/j.isci.2024.111478](https://doi.org/10.1016/j.isci.2024.111478) SUMMARY This review presents a thorough investigation of the role of CD47 in gastrointestinal cancers. We performed a comprehensive, in-depth review of over 100 preclinical and clinical studies focused on inhibiting CD47 . The research highlights the potential of targeted CD47 to enhance existing treatments by boosting the immune response to cancer cells. Considering the essential need to balance the toxicity and efﬁcacy of CD47 inhibition, our review emphasizes the need to optimize CD47 inhibitors. We also demonstrate the necessity of combining CD47 antibodies with conventional chemotherapy, radiotherapy, or other targeted therapies to enhance treatment effectiveness. Finally, we propose the integration of CD47-targeted therapies into treatment plans as a promising approach to reshape the therapeutic landscape of gastrointestinal cancers. Continued research in this ﬁeld holds great potential for improving the outcomes of gastrointestinal cancer patients and overcoming the challenges associated with this formidable spectrum of diseases. INTRODUCTION Cancer continues to be a leading cause of mortality worldwide, with gastrointestinal cancers being particularly devastating due to their high incidence and mortality rates.1 Major gastrointestinal cancers, classiﬁed under the 11th edition of the International Classiﬁcation of Diseases, include esophagus, stomach, colorectum, liver, gallbladder, and pancreas.2 According to GLOBOCAN 2022, gastrointestinal cancers accounted for approximately 2.97 million new cases and 2 .05 million deaths globally.3 Traditional treatments like chemotherapy, radiation therapy, and surgery often fall short, especially in advanced stages of gastrointestinal cancers. This is starkly evident in pancreatic cancer, which has become the third leading cause of cancerrelated deaths in regions like the European Union and the United States.4 ,5 These trends underscore the urgent need for more effective therapies. In response to these challenges, immunotherapy, particularly using immune checkpoint inhibitors targeting PD-1, has emerged as a promising approach.6 However, only a limited subset of patients, especially those exhibiting a high mutational burden or immune-related genetic abnormalities such as elevated microsatellite instability, demonstrate favorable responses to PD-1 inhibitors.7 CD47, which serves as a ‘‘don’t eat me’’ signal on cancer cells, thereby protecting them from macrophage-mediated phagocytosis, a mechanism distinctly different from the T cell modulation observed with PD-1 inhibitors, has emerged as a compelling new target in cancer immunotherapy.8 While CD47 inhibitors have demonstrated signiﬁcant potential in hematological malignancies, their application in solid tumors, particularly gastrointestinal cancers, has been limited.9 The modest efﬁcacy and unresolved toxicity issues of early CD47 inhibitors in these cancers suggest substantial room for improvement. This introduction aims to explore the landscape of CD47 as a novel therapeutic target within the broader context of gastrointestinal cancers, assessing both the achievements and limitations of current strategies.10 By providing a comprehensive overview of the existing clinical and preclinical data, this review will discuss the potential of CD47-targeted therapies

FAQs

What does CD47-targeted therapy aim to change in gastrointestinal cancer treatment?

The review focuses on inhibiting CD47 to enhance immune recognition and strengthen responses against cancer cells, potentially improving the effectiveness of existing therapies.

Why is optimizing CD47 inhibitors necessary?

Because CD47 inhibition requires balancing toxicity with efficacy, and early inhibitors in gastrointestinal cancers show modest effectiveness and unresolved safety concerns.

How can CD47 antibodies be used alongside other treatments?

The review emphasizes combining CD47 antibodies with conventional chemotherapy, radiotherapy, or other targeted therapies to enhance overall treatment effectiveness.

Sep 21, 2026

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