Publications by authors named "T Klinowska"
Article Synopsis
- The SERENA-2 trial investigates the efficacy of camizestrant, a new oral selective estrogen receptor degrader, compared to the traditional injectable SERD, fulvestrant, in treating advanced hormone receptor-positive breast cancer in post-menopausal women.
- This phase 2 trial includes patients who have experienced disease progression after previous endocrine therapies and assesses different dosages of camizestrant against fulvestrant, focusing on progression-free survival rates as the primary outcome.
- Conducted across 74 centers worldwide, the study also monitors the safety and side effects of the treatments among all participants who received at least one dose.
Article Synopsis
- Breast cancer is the most common cancer globally, with about 70% being estrogen receptor-positive (ER+), prompting research on drugs that can degrade or antagonize the ER.
- A review of patent applications from July 2021 to December 2023 examined 91 new drug candidates, classifying them into different types like acidic and basic SERDs and SERCAs.
- The approval of elacestrant, the first oral SERD, has spurred optimism in the development of new targeted treatments for ER+ breast cancer, even as research continues into other promising candidates.
Article Synopsis
- Targeting the estrogen receptor alpha (ERα) pathway is a proven strategy for treating estrogen receptor-positive (ER+) breast cancers, leading to the development of a new type of drug called a PROTAC designed to degrade ERα.
- In laboratory tests, this PROTAC showed strong effectiveness in degrading ERα and blocking its activity in breast cancer cells, but results did not match when tested in live models.
- The discrepancy is attributed to the PROTAC’s linker being metabolically unstable, which leads to the creation of competing metabolites that interfere with the drug's ability to degrade ERα; this emphasizes the importance of designing more stable PROTACs for better treatment outcomes.
Background: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation.
Patients And Methods: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion).
Article Synopsis
- Camizestrant, an oral selective estrogen receptor degrader (SERD), shows enhanced efficacy in treating estrogen receptor-positive (ER+) breast cancer compared to existing therapies, effectively targeting resistant cancer cells.
- In preclinical studies, camizestrant demonstrated significant ER degradation and antiproliferative effects in various breast cancer models, including those resistant to current treatments like fulvestrant.
- Combining camizestrant with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies increased antitumor effectiveness, suggesting a powerful approach to overcoming endocrine resistance in breast cancer patients.