Improving the predictive accuracy of efficacy evaluation using tumor orthotopic transplant and resection model

Front Pharmacol. 2024 Feb 27:15:1309876. doi: 10.3389/fphar.2024.1309876. eCollection 2024.

Abstract

Preclinical efficacy evaluation and tumor drug sensitivity analysis are two main applications of efficacy evaluation. Preclinical efficacy evaluation is to predict whether candidate drugs or therapies may improve patient outcomes in clinical trials. Tumor drug sensitivity analysis is an approach for the personalized evaluation and optimization of approved anti-cancer drugs and treatment regimens. Overall survival (OS) is the gold standard to evaluate the outcome of drugs or therapies in both clinical trials and clinical treatment. Many efficacy evaluation models, such as cell model, tumor cell-line transplant model, patient-derived tumor xenograft model, tumor organoid model, have been developed to assess the inhibitory effect of tested drugs or therapies on tumor growth. In fact, many treatments may also lead to malignant progression of tumors, such as chemotherapy, which can lead to metastasis. Therefore, tumor growth inhibition does not necessarily predict OS benefit. Whether it can prevent or inhibit tumor recurrence and metastasis is the key to whether drugs and therapies can improve patient outcomes. In this perspective, we summarize the current understanding of the pathological progression of tumor recurrence and metastasis, point out the shortcomings of existing tumor transplant models for simulating the clinical scenario of malignant progression of tumors, and propose five improved indicators for comprehensive efficacy evaluation to predict OS benefit using tumor orthotopic transplant and resection model. Improvement in the accuracy of efficacy evaluation will accelerate the development process of anti-cancer drugs or therapies, optimize treatment regimens to improve OS benefit, and reduce drug development and cancer treatment costs.

Keywords: OS benefit; efficacy evaluation model; neoadjuvant therapy and adjuvant therapy; preclinical efficacy evaluation; tumor drug sensitivity analysis; tumor local recurrence and distant metastasis; tumor orthotopic transplant and resection model.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (Grant Number 81900200), Natural Science Foundation of Jiangsu Province (Grant Number BK20190840), and Foundation of State Key Laboratory of Cell Biology (Grant Number SKLCB2018KF008).