Escalation and De-Escalation Strategies for Endocrine Therapy in Early-Stage Breast Cancer

Biologics, Год журнала: 2025, Номер Volume 19, С. 97 - 111

Опубликована: Март 1, 2025

Although adjuvant endocrine therapy (ET) greatly lowers the risk of recurrence and mortality in hormone receptor (HR)-positive early-stage breast cancer (EBC), more than 20% patients may experience relapses within 10 years, often manifesting as incurable distant metastases. To improve outcomes, ovarian function suppression (OFS) with gonadotropin-releasing agonists (GnRHa) added to tamoxifen or aromatase inhibitors like exemestane have shown significant disease-free survival (DFS) and, some cases, overall (OS) benefits. CDK4/6 inhibitors, a cornerstone metastatic HR-positive, HER2-negative (MBC), are now being explored EBC. Trials abemaciclib ribociclib promise high-risk For BRCA-mutant patients, PARP inhibitor olaparib, demonstrated OlympiA trial, significantly improved invasive DFS OS when used for one year. Conversely, de-escalation strategies also emerging. Recent studies suggest that younger premenopausal women low-risk disease safely interrupt ET after 18-30 months pursue pregnancy. Additionally, genomic tumor profiling is widely utilized decide on aggressiveness These advancements reflect shift toward personalized therapy, integrating targeted treatments optimizing OFS, balancing efficacy quality life through strategies. This tailored approach aims long-term outcomes HR-positive EBC patients.

Язык: Английский

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Pancreatic Cancer: Pathogenesis and Clinical Studies

MedComm, Год журнала: 2025, Номер 6(4)

Опубликована: Апрель 1, 2025

ABSTRACT Pancreatic cancer (PC) is a highly lethal malignancy, with pancreatic ductal adenocarcinoma (PDAC) being the most common and aggressive subtype, characterized by late diagnosis, progression, resistance to conventional therapies. Despite advances in understanding its pathogenesis, including identification of genetic mutations (e.g., KRAS, TP53, CDKN2A, SMAD4) dysregulated signaling pathways KRAS–MAPK, PI3K–AKT, TGF‐β pathways), effective therapeutic strategies remain limited. Current treatment modalities chemotherapy, targeted therapy, immunotherapy, radiotherapy, emerging therapies such as antibody–drug conjugates (ADCs), chimeric antigen receptor T (CAR‐T) cells, oncolytic viruses (OVs), vaccines, bispecific antibodies (BsAbs), face significant challenges. This review comprehensively summarizes these approaches, emphasizing their mechanisms, limitations, potential solutions, overcome bottlenecks. By integrating recent advancements outlining critical challenges, this aims provide insights into future directions guide development more for PC, specific focus on PDAC. Our work underscores urgency addressing unmet needs PDAC therapy highlights promising areas innovation field.

Язык: Английский

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HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

The emergence of drug resistance leading to cancer recurrence is one the challenges in treatment patients. Several mechanisms can lead resistance, including epigenetic changes. Histone deacetylases (HDACs) play a key role chromatin regulation through and are also involved resistance. control histone acetylation accessibility regulatory DNA sequences such as promoters, enhancers, super-enhancers known by which HDACs influence gene expression. Other targets that not histones contribute This review describes contribution that, some cases, may determine chemotherapy or other treatments.

Язык: Английский

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DREAM On, DREAM Off: A Review of the Estrogen Paradox in Luminal A Breast Cancers

Biomedicines, Год журнала: 2024, Номер 12(6), С. 1300 - 1300

Опубликована: Июнь 12, 2024

It is generally assumed that all estrogen-receptor-positive (ER+) breast cancers proliferate in response to estrogen and, therefore, examples of the estrogen-induced regression ER+ are paradoxical. This review re-examines paradox for Luminal A subtype cancers. The proliferative shown depend on level ER. Mechanistically, a window opportunity study pre-operative estradiol suggested with higher levels ER, could activate DREAM-MMB (Dimerization partner, Retinoblastoma-like proteins, E2F4, and MuvB-MYB-MuvB) pathway decrease proliferation. epithelium incidence during hormonal variations occur menstrual cycle at menopausal transition, respectively, suggest single hormone, either estrogen, progesterone or androgen, DREAM pathway, leading reversible cell arrest. Conversely, presence two hormones switch complex pro-proliferative pathway. Using publicly available data, we examine gene expression changes after aromatase inhibitors ICI 182,780 provide support hypothesis. suggests it might be possible integrate current therapies tumors within theoretical schema.

Язык: Английский

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Innovative Cancer Therapies: Targeting Oncogenic Pathways through Placental Immunology, PROTAC Technology, and Kinase Degradation

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(12), С. 2077 - 2079

Опубликована: Ноя. 11, 2024

Recent advancements in cancer therapy have led to groundbreaking approaches targeting critical oncogenic pathways. This Patent Highlight explores four essential patents that focus on modulating ligand–receptor interactions from placental immunology, degrading RAF proteins with MEK1/2 degraders, and employing PROTAC technology degrade Cyclin D, CDK4, CDK6 proteins. These innovations aim overcome traditional limitations address resistance cancers such as breast, lung, RAS-altered cancers. publication examines these inventions' mechanisms, findings, implications modern treatment.

Язык: Английский

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