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[New therapeutical strategies in metastatic hormone-dependent breast cancer]
Paul Vilquin1, Pascale Cohen2, Thierry Maudelonde1
1CHU de Montpellier, laboratoire de biologie cellulaire, 34295 Montpellier, France.
Abstract:
Hormone-dependent breast cancer is the first example of cancer treated by targeted therapy for more than 30 years. Blocking estrogen pathway was the first therapeutical strategy for this subtype of breast cancer, and remains the principle of current standard treatment. Despite the efficacy of drugs used in endocrine therapy, hormone resistance is a major problem for the management of patients with hormone-dependent breast cancer. In this review, we will discuss the development of strategies targeting the PI3K/Akt/mTOR pathway, CDK4/6 (Cyclin Dependent Kinase 4/6) and FGFR (Fibroblast Growth Factor Receptor) in hormone-dependent metastatic breast cancer (ER+). Recent results of clinical trials showed that combination of endocrine therapy with such pharmacological inhibitors is a promising strategy to overcome endocrine resistance. Mutated forms and isoforms of ERα have been recently discovered and its targeting could represent an therapeutic alternative. Future progress will focus on the identification of new compounds and combinations with other targeted therapies to improve the efficacy of such inhibitors in clinical practice.
Insights
Targeting hormone-dependent breast cancer with new therapies like PI3K/Akt/mTOR, CDK4/6, and FGFR inhibitors shows promise. Combining these with endocrine therapy may overcome resistance and improve patient outcomes.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Hormone-dependent breast cancer has been treated with targeted therapy for over 30 years, primarily by blocking the estrogen pathway.
- Endocrine therapy is a standard treatment, but hormone resistance remains a significant clinical challenge.
Purpose of the Study:
- To review emerging strategies targeting the PI3K/Akt/mTOR pathway, CDK4/6, and FGFR in hormone-dependent metastatic breast cancer (ER+).
- To discuss the potential of combining endocrine therapy with novel pharmacological inhibitors to overcome resistance.
Main Methods:
- Review of clinical trial results and recent discoveries in targeted therapy for hormone-dependent breast cancer.
- Discussion of novel therapeutic targets including mutated forms and isoforms of ERα.
Main Results:
- Combination of endocrine therapy with inhibitors of PI3K/Akt/mTOR, CDK4/6, and FGFR demonstrates promise in overcoming endocrine resistance.
- Discovery of mutated ERα forms suggests new therapeutic avenues.
Conclusions:
- Targeted therapies combined with endocrine therapy represent a promising strategy for managing hormone-dependent metastatic breast cancer.
- Future research will focus on identifying new compounds and combinations to enhance treatment efficacy.
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