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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments
Hon Yan Kelvin Yip1, Antonella Papa1
1Cancer Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.
Abstract:
Molecular alterations in cancer genes and associated signaling pathways are used to inform new treatments for precision medicine in cancer. Small molecule inhibitors and monoclonal antibodies directed at relevant cancer-related proteins have been instrumental in delivering successful treatments of some blood malignancies (e.g., imatinib with chronic myelogenous leukemia (CML)) and solid tumors (e.g., tamoxifen with ER positive breast cancer and trastuzumab for HER2-positive breast cancer). However, inherent limitations such as drug toxicity, as well as acquisition of de novo or acquired mechanisms of resistance, still cause treatment failure. Here we provide an up-to-date review of the successes and limitations of current targeted therapies for cancer treatment and highlight how recent technological advances have provided a new level of understanding of the molecular complexity underpinning resistance to cancer therapies. We also raise three basic questions concerning cancer drug discovery based on molecular markers and alterations of selected signaling pathways, and further discuss how combination therapies may become the preferable approach over monotherapy for cancer treatments. Finally, we consider novel therapeutic developments that may complement drug delivery and significantly improve clinical response and outcomes of cancer patients.
Insights
Targeted cancer therapies show promise but face resistance and toxicity. Advances reveal molecular complexities, suggesting combination therapies and novel developments may improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Precision medicine utilizes molecular alterations in cancer genes and signaling pathways for targeted treatments.
- Targeted therapies like imatinib, tamoxifen, and trastuzumab have succeeded in specific cancers but face limitations.
- Drug toxicity and acquired resistance mechanisms remain significant challenges in cancer treatment.
Purpose of the Study:
- To review the successes and limitations of current targeted cancer therapies.
- To highlight how technological advances enhance understanding of resistance mechanisms.
- To discuss future directions including combination therapies and novel drug developments.
Main Methods:
- Review of current literature on targeted cancer therapies.
- Analysis of molecular complexity and resistance mechanisms.
- Exploration of novel therapeutic developments and combination strategies.
Main Results:
- Targeted therapies have demonstrated efficacy but are hampered by toxicity and resistance.
- Recent technological advancements offer deeper insights into the molecular basis of therapeutic resistance.
- Combination therapies are proposed as a potentially superior approach to monotherapy.
Conclusions:
- Understanding molecular complexity is crucial for overcoming resistance to targeted cancer therapies.
- Combination therapies and novel therapeutic developments hold promise for improving clinical response and patient outcomes.
- Further research into cancer drug discovery based on molecular markers and signaling pathways is warranted.
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