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Targeting Different Pathways Using Novel Combination Therapy in Triple Negative Breast Cancer
Manzoor A Mir1, Hina Qayoom1, Umar Mehraj1
1Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, India.
Abstract:
Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer accounting for 15-20% of cases and is defined by the lack of hormonal receptors viz., estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth receptor 2 (HER2). Treatment of TNBC is more challenging than other subtypes of breast cancer due to the lack of markers for the molecularly targeted therapies (ER, PR, and HER-2/ Neu), the conventional chemotherapeutic agents are still the mainstay of the therapeutic protocols of its patients. Despite, TNBC being more chemo-responsive than other subtypes, unfortunately, the initial good response to the chemotherapy eventually turns into a refractory drug-resistance. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Thus, a cocktail of two or more drugs with different mechanisms of action is more effective and could successfully control the disease. Furthermore, combination therapy reveals more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance. Herein, we shed light on the novel combinatorial approaches targeting PARP, EGFR, PI3K pathway, AR, and wnt signaling, HDAC, MEK pathway for efficient treatment of high-grade tumors like TNBC and decreasing the onset of resistance.
Insights
Triple negative breast cancer (TNBC) treatment is challenging due to aggressive nature and drug resistance. Novel combination therapies targeting multiple pathways offer improved efficacy and reduced resistance for TNBC patients.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Triple negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 targets.
- Conventional chemotherapy is the primary treatment but often leads to acquired drug resistance.
- Monotherapy is ineffective for high-grade tumors like TNBC due to inherent genetic instability.
Purpose of the Study:
- To explore novel combinatorial therapeutic strategies for TNBC.
- To identify combination therapies that improve treatment efficacy and overcome chemoresistance.
- To investigate targeted pathways including PARP, EGFR, PI3K, AR, wnt signaling, HDAC, and MEK.
Main Methods:
- Review of current literature on TNBC treatment strategies.
- Analysis of emerging combinatorial approaches targeting specific molecular pathways.
- Focus on therapies designed to circumvent or delay drug resistance.
Main Results:
- Combination therapies demonstrate superior or equivalent efficacy compared to monotherapy.
- Targeting multiple pathways simultaneously can enhance anti-tumor effects.
- Reduced dosages in combination regimens may lower toxicity and chemoresistance.
Conclusions:
- Novel combination therapies targeting pathways like PARP, EGFR, PI3K, AR, wnt, HDAC, and MEK are promising for TNBC.
- Combination strategies are crucial for overcoming chemoresistance and improving patient outcomes.
- Further research into these combinatorial approaches is warranted for efficient TNBC treatment.
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