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Novel anticancer drug discovery
1Department of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, MS 38677, USA. mcjkb@olemiss.edu
Abstract:
There is at present, much optimism about the possibility of finding selective anticancer drugs that will eliminate the cytotoxic side effects associated with conventional cancer chemotherapy. This hope is based on uncovering many novel molecular targets that are 'cancer-specific', which will allow the targeting of cancer cells while normal cells are spared. Thus far, encouraging results have been obtained with several of these novel agents at the preclinical level, and clinical trials have begun. These targets are involved at one level or more in tumor biology, including tumor cell proliferation, angiogenesis and metastasis. Novel targets for which advances are being made include the following: growth factor receptor tyrosine kinases such as the epidermal growth factor receptor and HER-2/neu (proliferation); the vascular endothelial growth factor receptor and the basic fibroblast growth factor receptor (angiogenesis); the oncogenic GTP-binding protein Ras (especially agents targeting Ras farnesylation, farnesyltransferase inhibitors) (proliferation); protein kinase C (proliferation and drug resistance); cyclin-dependent kinases (proliferation); and matrix metalloproteinases and angiogenin (angiogenesis and metastasis). Less explored, but potentially useful targets include the receptor tyrosine kinase platelet-derived growth factor receptor, mitogen-activated protein kinase cascade oncogenes such as Raf-1 and mitogen-activated protein kinase kinase, cell adhesion molecules such as integrins, anti-apoptosis proteins such as Bcl-2, MDM2 and survivin, and the cell life-span target telomerase.
Insights
Researchers are developing novel anticancer drugs targeting specific molecules to reduce chemotherapy side effects. These targeted therapies focus on cancer cell proliferation, angiogenesis, and metastasis, showing promise in preclinical studies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Conventional chemotherapy causes cytotoxic side effects.
- Novel molecular targets specific to cancer cells offer a promising alternative.
- Targeted therapies aim to spare normal cells while eliminating cancer cells.
Purpose of the Study:
- To review novel molecular targets for selective anticancer drug development.
- To discuss the role of these targets in tumor biology (proliferation, angiogenesis, metastasis).
- To highlight advances in targeting specific pathways and proteins in cancer.
Main Methods:
- Review of preclinical and clinical data on novel anticancer agents.
- Identification and categorization of molecular targets involved in cancer progression.
- Analysis of targets including growth factor receptors, kinases, GTP-binding proteins, and cell adhesion molecules.
Main Results:
- Several novel targets are being investigated, including growth factor receptor tyrosine kinases (EGFR, HER-2/neu), VEGF/bFGF receptors, Ras pathway proteins, protein kinase C, and cyclin-dependent kinases.
- Targets involved in angiogenesis and metastasis, such as matrix metalloproteinases and angiogenin, are also discussed.
- Emerging targets include platelet-derived growth factor receptor, MAPK pathway components, integrins, anti-apoptosis proteins (Bcl-2, MDM2, survivin), and telomerase.
Conclusions:
- Significant optimism exists for developing selective anticancer drugs with reduced side effects.
- Targeted therapies offer a new paradigm in cancer treatment by focusing on cancer-specific molecular pathways.
- Continued research into these novel targets holds potential for improved cancer patient outcomes.