Background: Multidrug resistance (MDR) is the resistance of cancer cells against a variety
of currently used antineoplastic agents with diverse structural scaffolds and different anticancer mechanisms.
It has been recognized as one of the major impediments to the successful treatment of cancer,
leading to the metastasis and relapse of malignant diseases.
Introduction: Collateral sensitivity (CS) is the characteristic of certain chemicals to kill the drugresistant
sublines selectively over the parental cell lines from which the resistant cells were generated.
The research and development of new drug candidates with collateral sensitivity will be an efficient
approach to conquer multidrug resistance in cancer. We aim to provide an update on the discovery of
natural products with collateral sensitivity.
Results and Conclusion: The review focused on the characterized anticancer natural products and
their derivatives with collateral sensitivity, their working mechanisms, and related structure-activity
relationships, emphasizing recently identified CS compounds. According to their structural features,
these MDR-targeting compounds were mainly classified into the following categories: flavonoids,
terpenoids, stilbenes, alkaloids and quinones. The exploration of molecular mechanisms of collateral
sensitivity and structural features of anticancer agents with collateral sensitivity provided an effective
approach for the clinic treatment of MDR in cancer.