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Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas
Jillian Cathcart1, Ashleigh Pulkoski-Gross1, Jian Cao2
1Department of Cellular and Molecular Pharmacology, Stony Brook University, Stony Brook, NY 11794.
Abstract:
Since the identification of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, as being a driving factor for cancer progression and patient prognosis, MMPs have been studied extensively. Although early programs targeting MMPs were largely unsuccessful in clinical trials, they remain a viable and highly desirable therapeutic target based on preclinical studies and their role in disease progression. As information regarding the structure and function of these proteinases is compiled and biotechnology evolves, tools to develop better inhibitors is within our grasp. Improved methods for high throughput screening and in silico drug design programs have identified compounds which are highly potent, have high binding affinities, and exhibit favorable pharmacokinetic profiles. More recently, advances in drug delivery methods or compounds which bind outside the active site have brought new light to the field. In this review, we highlight the role of MMPs in cancer, clinical trials for MMP inhibitors, and novel approaches to targeting MMPs in cancer.
Insights
Matrix metalloproteinases (MMPs) are key to cancer progression. Despite early trial failures, novel drug design and delivery methods offer new hope for developing effective MMP inhibitors for cancer therapy.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases implicated in cancer progression and patient prognosis.
- Despite early clinical trial setbacks, MMPs remain a significant therapeutic target due to their established role in disease.
- Ongoing research into MMP structure and function, coupled with biotechnological advancements, is crucial for developing effective inhibitors.
Purpose of the Study:
- To review the critical role of MMPs in cancer development.
- To analyze the outcomes of clinical trials targeting MMPs.
- To explore novel strategies for targeting MMPs in cancer therapy.
Main Methods:
- Literature review of MMPs in cancer progression.
- Analysis of clinical trial data for MMP inhibitors.
- Evaluation of emerging drug design and delivery technologies.
Main Results:
- Early MMP inhibitor trials faced challenges, impacting clinical success.
- Preclinical studies consistently demonstrate MMPs' involvement in cancer.
- Advanced screening and computational methods identify potent inhibitors with favorable profiles.
Conclusions:
- MMPs are crucial targets in oncology.
- Novel approaches, including allosteric inhibitors and advanced drug delivery, show promise.
- Targeting MMPs remains a viable strategy for cancer treatment development.
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