Piqray (alpelisib) / Novartis - LARVOL DELTA

management of an adrenal cortical carcinoma induced non-islet cell tumor hypoglycemia: a case report (ENDO 2025) - "She was started on adjuvant mitotane, and chemotherapy (cisplatin, etoposide, and doxorubicin) which induced cardiomyopathy...Osilodrostat was initiated for Cushing syndrome...Patient had recurrent severe hypoglycemic episodes, which were refractory to increasing carbohydrate intake, high-dose prednisone, and octreotide...She also received pasireotide 60mg and diazoxide 5mg/kg every 8 hours...Upon applying for alpelisib approval, her clinical status rapidly declined, and she died after 3 months of NITCH diagnosis...IGF2-mediated hypoglycemia was refractory to numerous therapeutic interventions, including paseriotide, pembrolizumab, olaparib, ivosidenib, and cabozantinib. This case emphasizes rare manifestations of metastatic ACC and limitations of existing medical therapies for NITCH."

Case report • Clinical • Adrenal Cortex Carcinoma • Cardiomyopathy • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypoglycemia • Metabolic Disorders • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF1 • IGF2

Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus Olaparib Versus Chemotherapy in Platinum-Resistant or Platinum-Refractory High-Grade Serous Ovarian Cancer Without BRCA Mutation. (PubMed, J Clin Oncol) - "The primary objective, PFS improvement, was not met in EPIK-O. No new or unexpected adverse events were observed. Biomarker analyses provided new insights for responders to alpelisib + olaparib."

Journal • Platinum resistant • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

Tipifarnib (TIP) and alpelisib (ALP) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 1 results from KURRENT-HN (ESMO 2025) - No abstract available

Metastases • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Alpelisib (ALP) + fulvestrant (FUL) therapy in patients (pts) with PIK3CA-mutated (mut) HR+, HER2− advanced breast cancer (ABC) who progressed on/after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + aromatase inhibitor (AI): Primary analysis (PA) of EPIK-B5 study (ESMO 2025) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

In Silico Discovery of a Novel Potential Allosteric PI3Kα Inhibitor Incorporating 3-(2-Chloro-5-fluorophenyl)isoindolin-1-one to Target Head and Neck Squamous Cell Carcinoma. (PubMed, Biology (Basel)) - "Compared to ATP-competitive PI3Kα inhibitors such as Alpelisib, the allosteric inhibitor RLY-2608 exhibits enhanced selectivity for mutant PI3Kα while minimizing the inhibition of wild-type PI3Kα, thereby reducing side effects such as hyperglycemia. Through integrated approaches, including molecular docking studies, target validation, druggability evaluation, molecular dynamics simulations, and metabolic pathway and metabolite analyses, we successfully identified a promising novel allosteric PI3Kα inhibitor, H-18 (3-(2-chloro-5-fluorophenyl)isoindolin-1-one). H-18 has not been previously reported as a PI3Kα inhibitor, and provides an excellent foundation for subsequent lead optimization, offering a significant starting point for the development of more potent PI3Kα allosteric inhibitors."

IO biomarker • Journal • Diabetes • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PIK3CA

Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells. (PubMed, Antioxidants (Basel)) - "Exposure to the redox-disrupting agent erastin revealed key metabolic vulnerabilities but failed to produce lasting growth suppression. Combinatorial treatments with methotrexate or alpelisib significantly impaired proliferation and triggered marked metabolic shifts...Notably, cells that resumed growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways, along with elevated expression of genes linked to survival, proliferation, and migration. These findings establish serine metabolism as a functional biomarker of metabolic plasticity and adaptive resilience in pancreatic cancer, suggesting that targeting this adaptive axis may enhance therapeutic efficacy."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

INAVO121: A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (clinicaltrials.gov) - P3 | N=400 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2029 ➔ Jun 2026

Trial primary completion date • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2 • PIK3CA

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Treatment of Ovarian Clear Cell Carcinoma: A Case of Successful Management With Targeted Therapies. (PubMed, Case Rep Obstet Gynecol) - "Case: A 56-year-old woman was diagnosed with ovarian clear cell carcinoma and treated with surgical management as well as carboplatin and paclitaxel...A durable response was achieved first with alpelisib, chosen based on genomic testing. When progression occurred on this agent, a partial disease response was achieved with the combination of nivolumab and ipilimumab. The use of targeted therapies as well as the combination of nivolumab and ipilimumab is a promising option in advanced and recurrent cases of ovarian clear cell carcinoma."

Journal • Clear Cell Carcinoma • Oncology • Ovarian Cancer • Solid Tumor

Comparison of PI3K Inhibitor Versus AKT Inhibitor on Hyperglycemia with Continuous Glucose Monitoring in Metastatic Breast Cancer (ENDO 2025) - "Clinical Case: A 59-year-old woman with a history of T2DM, diastolic heart failure, and metastatic breast cancer (ER+, PR+, HER2+), was started on alpelisib 250 mg daily in combination with fulvestrant after a liquid biopsy analyzing tumor biomarkers confirmed a PIK3CA (H1047R) mutation. Her diabetes was previously well-managed with metformin extended release, yielding a glucose management indicator (GMI) of 5.6%...Alpelisib was stopped and empagliflozin 10 mg daily was started, and glycemia normalized four days later (average glucose of 120 mg/dL)... This case underscores the pronounced hyperglycemic effects of alpelisib, emphasizing the need for diligent monitoring and management of glycemia. Options to manage hyperglycemia from PI3K inhibitors are limited as medications binding to the insulin receptor can activate the PI3K tissue proliferation cascade. The transition to capivasertib improved her glycemic control and highlights the importance of individualized cancer..."

Metastases • Breast Cancer • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • HER2 Breast Cancer • HER2 Positive Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • HER-2 • IR • PGR • PIK3CA

Managing Capivasertib Induced Hyperglycemia in a Patient with Pre-Existing Type 2 Diabetes (ENDO 2025) - "The AKT inhibitor, capivasertib, has been approved by the US Food and Drug Administration (FDA) in combination with fulvestrant in the treatment of HR+, HER2- breast cancer...Clinical Case: A 71-year-old woman with class I obesity, type 2 diabetes, and metastatic ER+/PR+/HER2- breast cancer with osseous metastases and PIK3CA mutation, was started on alpelisib... Therapeutic agents that target the PI3K/AKT/mTOR signaling pathway are increasingly common in breast cancer treatment. Hyperglycemia is prevalent with aleplisib, the first FDA approved PI3K inhibitor, occurring in 64% of patients in the SOLAR-1 trial. While management of PI3K inhibitor associated hyperglycemia remains under investigation, low carbohydrate diets and oral antiglycemic agents have been reported."

Clinical • Breast Cancer • Diabetes • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Metabolic Disorders • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • HER-2 • PGR • PIK3CA

Challenges in Hyperglycemia Management in a Patient Treated With a Phosphatidylinositol 3-Kinase Inhibitor (ENDO 2025) - "Hyperglycemia is an on-target side effect of PI3K inhibitors that presents unique challenges in glycemic management for patients receiving these therapies.Clinical Case: A 72-year-old woman with a history of type 2 diabetes on empagliflozin monotherapy, hypertension, hyperlipidemia, and uterine clear cell carcinoma presented with shortness of breath, hyperglycemia, and word finding difficulty. She had been started on the PI3K inhibitor alpelisib 300 mg daily eight days prior to admission and developed worsened hyperglycemia...Pioglitazone, one of the preferred options as it does not interfere with the PI3K pathway, was not recommended due to recent history of Takotsubo cardiomyopathy and reduced ejection fraction... Hyperglycemia is an on-target side effect of PI3K inhibitors. Metformin, SGLT2 inhibitors and thiazolidinediones are preferred medications to treat PI3K-induced hyperglycemia because their mechanism of action does not affect the PI3K signaling pathway...."

Clinical • Cardiomyopathy • Cardiovascular • Clear Cell Carcinoma • Diabetes • Dyslipidemia • Hematological Malignancies • Hypertension • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus

Targeted Treatment With Alpelisib for Papillary Intralymphatic Angioendothelioma Associated With Somatic PIK3CA Mosaicism. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • PIK3CA

JAK2 Inhibition Augments the Anti-Proliferation Effects by AKT and MEK Inhibition in Triple-Negative Breast Cancer Cells. (PubMed, Int J Mol Sci) - "Among the four JAK2 inhibitors evaluated (fedratinib, cerdulatinib, peficitinib, and filgotinib), fedratinib significantly inhibited the proliferation of TNBC cells with IC50 values below 2 μM...Notably, combining ceduratinib with either cobimetinib (MEK inhibitor) and ipatasertib (AKT inhibitor) or trametinib (MEK inhibitor) and alpelisib (PI3K inhibitor) mimicked the effects of fedratinib on the cell proliferation, MYC and cyclin D1 suppression, and pro-apoptotic protein induction. These finding suggest that JAK2 inhibition enhances the anticancer effects of concurrent MEK/ERK and PI3K/AKT pathway inhibition, while JAK2 inhibition alone shows minimal efficacy in TNBC cells."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCND1

Drug Repurposing Targeting miRNA-mRNA Networks to Mitigate Areca Nut-Induced Head and Neck Cancer. (PubMed, Biomed J) - "This integrative approach elucidates areca nut-driven carcinogenesis through miRNA-mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • MIR410

Umbrella Trial of Subtype-Targeted Therapies in ER+/HER2- Breast Cancer (clinicaltrials.gov) - P2 | N=19 | Suspended | Sponsor: Stanford University | Active, not recruiting ➔ Suspended

Trial suspension • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Alpelisib for Long-term Management of Tumor-Induced Hypoglycemia. (PubMed, AACE Endocrinol Diabetes) - "Alpelisib, a small-molecule phosphatidylinositol 3-kinase inhibitor, may blunt the hypoglycemic effect of excess insulin and proinsulin by decreasing glucose transport and increasing glycogenolysis and gluconeogenesis. Alpelisib appears to be effective and well tolerated for long-term treatment of TIH."

Journal • Gastroenterology • Hypoglycemia • Oncology • IGF2

Somatic Mutations in Middle East and North Africa (MENA) Breast Cancer Patients: A Systematic Review. (PubMed, Oncologist) - "This study reveals both shared and distinct somatic mutation patterns in MENA breast cancer patients compared to Western populations. The high prevalence of clinically actionable mutations, particularly in PIK3CA and DNA repair genes, presents immediate opportunities for implementing targeted therapies across the region. Our findings underscore the urgent need for establishing a MENA Breast Cancer Genomics Consortium to standardize sequencing protocols, develop locally validated gene panels, and create regional variant databases that capture the unique mutation spectrum of these populations. This comprehensive genomic landscape of breast cancer in the MENA region addresses a critical gap in global cancer genomics, ultimately improving outcomes for a historically underrepresented patient population."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • IL1B • KLF6 • PIK3CA • PTEN • TP53

Exercise-related immune gene signature for hepatocellular carcinoma: machine learning and multi-omics analysis. (PubMed, Front Immunol) - "The high-risk group had higher macrophage abundance and immune escape ability, as well as greater sensitivity to Afatinib and Alpelisib. We identified key EIGs and constructed an EIGPS that can effectively predict the prognosis of HCC, which offers avenues for better personalized treatments."

Biomarker • Gene Signature • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CYP2C9 • ENO1 • SLC2A1

Development of a novel PIK3CA-mutated pancreatic tumor mouse model and evaluation of the therapeutic effects of a PI3K inhibitor. (PubMed, PLoS One) - "Combination treatment with alpelisib and the MEK inhibitor PD98059 significantly inhibited cell proliferation. These data indicate that PIK3CA mutation may be oncogenic in PDAC and that PI3K inhibitors can be effective against such tumors. Dual inhibition of the PI3K/AKT and MEK/ERK pathways may enhance therapeutic effects in PI3K/AKT-activated pancreatic tumors."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Transplantation • PIK3CA

A computational study of cardiac glycosides from Vernonia amygdalina as PI3K inhibitors for targeting HER2 positive breast cancer. (PubMed, J Comput Aided Mol Des) - "Molecular docking results indicated that these three compounds exhibited stronger and more stable interactions with the PIK3CA receptor compared to alpelisib, a known PIK3CA inhibitor. Furthermore, molecular dynamics simulations revealed that VG-10 had the lowest binding free energy, as determined by MM-GBSA analysis. The findings of this study provide a foundational basis for preclinical and clinical investigations aimed at developing PI3K inhibitors derived from cardiac glycosides of V. amygdalina for the treatment of HER2+ breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • mTOR • PIK3CA

TEK-related venous malformation of the orofacial region: report of a case with multidisciplinary treatment guided by molecular diagnosis. (PubMed, Oral Surg Oral Med Oral Pathol Oral Radiol) - "Alpelisib is a phosphatidylinositol 3-kinase inhibitor recently shown to be effective for treating VMs with PIK3CA or TEK mutations...Molecular diagnostics and targeted agents have ushered in a new era of precision medicine for VMs. It is important for pathologists and clinicians to be aware of molecular-guided therapy as delivered via a multidisciplinary team-based approach for optimal management of patients with VMs."

Journal • PIK3CA • TEK

EPIK-B2: Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation (clinicaltrials.gov) - P3 | N=20 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Activating PIK3CA mutations in adipose-derived stem cells drive mutant-like phenotypes of wild-type cells in macrodactyly. (PubMed, Cell Death Dis) - "These findings demonstrated that activating PIK3CA mutation alters the paracrine characteristics of Mac-ADSCs and reshapes the microenvironment of macrodactyly, driving adjacent wild-type cells to exhibit mutant-like phenotypes. Targeting PIK3CA with BYL-719 could influence the progression of macrodactyly by inhibiting the paracrine signaling of Mac-ADSCs."

Journal • PIK3CA

Preclinical Evaluation of Novel Phosphoinositide 3-Kinase Inhibitors: Antitumor Activity and Toxicity Assessment (EACR 2025) - "In the first step, cells were exposed to the inhibitors and Alpelisib (a PI3K inhibitor) at a single dose, followed by a five-dose step to determine IC50 values using the MTS assay... VL336 and VL311 showed significant in vitro efficacy in 2D, 3D, and patient-derived CRC models, highlighting their therapeutic potential, warranting further investigation of their therapeutic potential, clinical applicability and toxicity."

Preclinical • Colorectal Cancer • Oncology • Solid Tumor • PIK3CA