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Emerging treatment combinations: integrating therapy into clinical practice
1The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903-2681, USA. wongse@umdnj.edu
Purpose:
To review data supporting the effectiveness of emerging treatment options for metastatic breast cancer.
Summary:
Recent research has focused on several signal-transduction pathways important in the pathogenesis of breast cancer. Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that is involved in cell growth and survival. Everolimus, an orally active inhibitor of mTOR, has demonstrated promising efficacy results and a favorable safety profile in initial studies. Epidermal growth factor receptor (EGFR), a cell-surface molecule that has been implicated in the pathogenesis of breast cancer, may also be important in the emergence of resistance to endocrine therapy. Initial clinical studies have suggested that EGFR inhibitors such as gefitinib may delay the development of resistance to endocrine therapy in patients with breast cancer when given concurrently with tamoxifen or an aromatase inhibitor. Finally, considerable recent research has examined the role of epigenetic gene silencing, in which acetylation or deacetylation of DNA modifies the expression of tumor-suppressing genes. The enzyme histone deacetylase (HDAC) suppresses gene transcription by modifying chromatin into a more compact form. HDAC inhibitors have emerged as a potential new treatment option for several cancer types, including breast cancer. The HDAC inhibitor vorinostat has recently been examined in combination with other treatments, including cytotoxic agents and bevacizumab, for the treatment of breast cancer. In one small Phase I and II study, first-line treatment with the combination of vorinostat, paclitaxel, and bevacizumab produced objective responses (partial or complete) in more than 50% of patients with recurrent or metastatic breast cancer.
Conclusions:
Although the results of the described studies are promising, randomized controlled clinical trials are needed to better understand the efficacy and safety of emerging treatment options for patients with metastatic breast cancer.
Insights
Emerging treatments targeting signal-transduction pathways show promise for metastatic breast cancer. Further randomized trials are essential to confirm the efficacy and safety of these novel therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Metastatic breast cancer (MBC) treatment is evolving with a focus on targeted therapies.
- Signal-transduction pathways play a critical role in breast cancer development and progression.
- Resistance to endocrine therapy is a significant clinical challenge in MBC management.
Purpose of the Study:
- To review emerging treatment options for metastatic breast cancer.
- To evaluate the potential of novel targeted therapies and epigenetic modifiers.
- To assess the role of signal-transduction inhibitors in overcoming resistance mechanisms.
Main Methods:
- Review of recent research on signal-transduction pathways and epigenetic modifications in breast cancer.
- Analysis of data on mammalian target of rapamycin (mTOR) inhibitors, such as everolimus.
- Examination of epidermal growth factor receptor (EGFR) inhibitors in combination with endocrine therapy.
- Evaluation of histone deacetylase (HDAC) inhibitors, such as vorinostat, in combination regimens.
Main Results:
- Everolimus, an mTOR inhibitor, shows promising efficacy and a favorable safety profile in initial studies.
- EGFR inhibitors (e.g., gefitinib) may delay endocrine therapy resistance when combined with tamoxifen or aromatase inhibitors.
- Vorinostat, an HDAC inhibitor, in combination with paclitaxel and bevacizumab, achieved objective responses in over 50% of patients with recurrent/metastatic breast cancer in a Phase I/II study.
Conclusions:
- Emerging therapies targeting mTOR, EGFR, and epigenetic pathways offer new avenues for MBC treatment.
- Initial findings for everolimus, EGFR inhibitors, and vorinostat combinations are encouraging.
- Randomized controlled trials are necessary to validate the efficacy and safety of these novel approaches in MBC.
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