Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

This review offers an expert perspective on biomarkers, CDK4/6 inhibitor efficacy, and therapeutic approaches for managing hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (ABC), particularly after progression. Key trials have demonstrated that combining inhibitors with endocrine therapy (ET) significantly improves progression-free survival (PFS), median durations ranging from 14.8 to 26.7 months, overall (OS), reaching up 53.7 months. Actionable such as PIK3CA ESR1 mutations, emerged pivotal tools guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib elacestrant emphasizing important role biomarkers in guiding selection therapy. overview aims provide clinicians a practical up-to-date framework inform decisions improve patient care context this challenging disease. Additionally, we emerging novel strategies address difficult clinical landscape.

Language: Английский

---

An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Introduction . The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role treatment resistance. This pathway's involvement carcinogenesis its link to resistance underscores the significance of targeting it BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due toxicity issues that hinder their development.

Language: Английский

---

Inavolisib: First Approval

Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

---

Next-generation sequencing for PTEN testing in HR+/HER2˗ metastatic breast cancer

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104626 - 104626

Published: Feb. 1, 2025

Language: Английский

---

Novel drugs approved by the EMA, the FDA and the MHRA in 2024: A year in review

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract In the past year, European Medicines Agency (EMA), Food and Drug Administration (FDA) Healthcare Products Regulatory (MHRA) authorised 53 novel drugs. While 2024 harvest is not as rich in 2023, when 70 new chemical entities were approved, number of ‘orphan’ drug authorisations (21) similar to that 2023 (24), illustrating dynamic development therapeutics areas unmet need. The approvals protein (15) advanced therapy medicinal products (ATMPs, 6) indicate a sustained trend also noticeable drugs reviewed this journal last year (16 11, respectively). Clearly, most striking characteristic yield creative pharmacological design, which allows these medicines employ approach target disease. Some notable examples are first successfully using ‘dock‐and‐block’ mechanism inhibition (zenocutuzumab), approved for schizophrenia designed an agonist M 1 /M 4 muscarinic receptors (xanomeline), biparatopic antibody (zanidatamab), binding two distinct epitopes same molecule, haemophilia instead relying on external supplementation clotting factors, restores Factor Xa activity by inhibiting TFPI (marstacimab), or ever direct telomerase inhibitor (imetelstat) reprogrammes oncogenic drive tumour cells. addition, impressive percentage class (28 out 53% total) substantial can be considered disease agnostic, indicating possibility future extensions their use additional indications. demonstrates therapeutic potential innovative effective targeting intractable disorders addresses crucial, needs.

Language: Английский

---

In silico discovery of a novel potential allosteric PI3Kα inhibitor incorporating 2-oxopropyl urea targeting head and neck squamous cell carcinoma

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 28, 2025

Head and neck squamous cell carcinoma (HNSCC) is the most common head cancer highly aggressive heterogeneous. Targeted therapy still main treatment method used in clinic due to lower side effect personalized medication. In order discover novel effective drugs with low against HNSCC, we analyzed genes related found that PIK3CA was expressed tumor tissues often experienced mutations, leading excessive activation of phosphoinositide 3-kinase alpha (PI3Kα), promoting development HNSCC. The allosteric PI3Kα inhibitor STX-478 inhibits growth hotspot mutations shows prominent efficacy on human HNSCC xenografts without displaying metabolic dysfunction observed Alpelisib. These open site more readily, increasing selectivity for mutant PI3Kα. cleverly avoids ATP competitive inhibitors. So, structure optimized based interaction mechanism between Then, virtual screening, binding mode research, target verification, physical chemical properties, pharmacokinetic properties stabilities ligand-PI3Kα complexes were evaluated by computer technologies (scaffold hopping, cdocker, SuperPred, SwissTarget prediction, Lipinski's rule five, ADMET MD simulation). Finally, J-53 (2-oxopropyl urea compound) excellent selected. not only formed H-bonds key amino acids, but its unique -C(O)CH3 could also form ILE1019, making it stably bound contributing activity. After SciFinder had value further study. This study suggested be as potential inhibitors PI3Kα, provides valuable information subsequent drug discovery

Language: Английский

---

Targeted and cytotoxic inhibitors used in the treatment of breast cancer

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107534 - 107534

Published: Dec. 1, 2024

Breast cancer is the most commonly diagnosed malignancy and fifth leading cause of deaths worldwide. Surgery radiation therapy are localized therapies for early-stage metastatic breast cancer. The management determined in large part by HER2 (human epidermal growth factor receptor 2), HR (hormone receptor), ER (estrogen PR (progesterone receptor) status. Our views evolving as its molecular hallmarks examined, which now include immunohistochemical markers (ER, PR, HER2, proliferation marker protein Ki-67), genomic (BRCA1/2 PIK3CA), immunomarkers (tumor-infiltrating lymphocytes PDL1). About two-thirds malignancies HR-positive/HER2-negative; accordingly, endocrine-based a major treatment option these patients. Hormonal or endocrine includes selective estrogen modulators (SERMs) such raloxifene, tamoxifen toremifene, estrogen-receptor degraders (SERDs) including elacestrant fulvestrant, aromatase inhibitors anastrozole, letrozole, exemestane. A variety cytotoxic chemotherapeutic agents used to treat HR-negative These taxanes (docetaxel, nab-paclitaxel, paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating (carboplatin, cisplatin, cyclophosphamide), drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors treated 5-10 years chemotherapy. For patients cancer, standard first-line follow-up options targeted approaches CDK4/6 inhibitors, PI3K PARP anti-PDL1 immunotherapy, depending on tumor type profile.

Language: Английский

---

Identifying and managing adverse prognosis biomarkers among advanced luminal breast cancer patients: what have we learned?

European Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 115228 - 115228

Published: Jan. 1, 2025

Language: Английский

---

Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity its various subtypes. This study aimed to investigate differential expression genes and miRNAs involved in PI3K/AKT/mTOR signaling pathway, critical regulator progression. We analyzed tumor tissues from five breast subtypes-luminal A, luminal B HER2-negative, HER2-positive, triple-negative (TNBC)-and compared them with non-cancerous tissues. Microarray qRT-PCR techniques were employed profile mRNAs miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed statistical significance threshold (p) < 0.05. identified several upregulated across all subtypes, TNBC HER2-positive cancers showing most significant changes. Key such as COL1A1, COL4A1, PIK3CA, PIK3R1, mTOR found be overexpressed, correlating increased aggressiveness. miRNA revealed that miR-190a-3p, miR-4729, miR-19a-3p potentially regulate these genes, influencing pathway. For instance, reduced miR-190a-3p may contribute overexpression PIK3CA other pathway components, enhancing metastatic potential. Our findings suggest regulators play crucial roles progression, particularly aggressive subtypes like TNBC. The hold potential biomarkers for diagnosis treatment, but further validation functional studies is required. provides foundation targeted therapies at modulating this improve outcomes.

Language: Английский

---

Inavolisib Therapy in Advanced Breast Cancer

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(3), P. 310 - 311

Published: Jan. 15, 2025

Language: Английский

---