Abstract
Eribulin, a synthetic marine based drug has received extensive attention recently due to its promising anticancer activities against a wide variety of cancer types as evidenced by preclinical and clinical data. Eribulin is predominantly shown to exhibit microtubule inhibitory activity, however recent reports indicate that it acts via multiple molecular mechanisms targeting both the cancer cells as well as the tumor microenvironment. In this review, a comprehensive account on various modes of action of eribulin on cancer cells is presented along with important clinical aspects in the management of cancer through a comprehensive literature review. We have also highlighted approaches including combination therapy to improve the efficacy of eribulin in cancer treatment. Currently, eribulin is used to treat heavily pretreated patients with metastatic breast cancer, for which it gained FDA approval a decade ago and more recently, it has been approved for treating anthracycline-pretreated patients with metastatic liposarcoma. Novel therapeutic strategies should aim at resolving the toxicity and resistance conferred due to eribulin treatment so that it could be integrated in the clinics as a first-line treatment approach.
Highlights
Over the recent years, significant decrease in the mortality due to cancer has been observed globally [1]
The results showed that the epithelial mesenchymal transition (EMT) pathway was activated with significantly altered expression between the drugs for breast and endometrial cancers, but not for ovarian cancer [43]
Dose scheduling studies with eribulin on MDA-MB-435 breast, HT-1080 fibrosarcoma, U251, glioblastoma, SR475 head and neck cancer, SK-LMS-1 leiomyosarcoma, NCI-H322M and NCI-H522 nonsmall cell lung cancer (NSCLC), PANC-1 pancreatic cancer, and NCI-H82 small cell lung cancer (SCLC) models showed that maximal efficacy and minimal toxicity is achieved with moderate intermittent dosing [21]
Summary
Significant decrease in the mortality due to cancer has been observed globally [1]. One of the plausible reasons could be better understanding of molecular mechanisms underlying different types of cancers. Such knowledge has led to the current era of targeted therapies and precision medicine. In spite of potent anticancer properties on a wide variety of cancers [7], Halichondrin B could not be developed as a therapeutic drug due to its limited availability and complicated isolation process from the marine source. In this review a detailed account on different molecular mechanisms of eribulin unraveled until recently along with preclinical and clinical evidences for its potent anticancer activity are provided along with its possible implications as an effective drug
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