Piqray (alpelisib) / Novartis - LARVOL DELTA

Rapidly Progressive AKI After Alpelisib Therapy: Suspected Acute Interstitial Nephritis (KIDNEY WEEK 2026) - "Alpelisib was discontinued, and prednisone 60 mg daily was initiated. Rapid improvement following drug discontinuation and corticosteroid therapy favored a reversible immune-mediated process rather than acute tubular injury. The absence of severe hemodynamic instability or alternative nephrotoxic exposures further supported a medication-associated etiology."

Acute Kidney Injury • Breast Cancer • Eosinophilia • Immunology • Nephrology • Renal Disease • Solid Tumor

mTOR Signaling: A Key Player in X-Linked Alport Syndrome Disease Progression (KIDNEY WEEK 2026) - "Because rapamycin can have undesirable side effects in humans, we repeated the experiment using rapamycin and three alternative interventions (meclizine, alpelisib, and fisetin) starting at 4-weeks of age...Results Glomerular filtration rate, a measure of kidney function, showed no significant treatment effects, while albumin-to-creatinine ratio, a measure of kidney damage, demonstrated that rapamycin, meclizine, and fisetin significantly reduced kidney damage. Conclusion Together, these findings show that targeting specific components of the mTOR pathway can reduce kidney damage in XLAS mice and highlight mTOR pathway modulation as a promising therapeutic strategy for Alport-related kidney disease."

Genetic Disorders • Nephrology • Renal Disease • COL4A5 • PIK3R1

PRAC endorsed an extension of indication for Piqray in combination with fulvestrant for postmenopausal women and men with HR-positive, HER2-negative, locally advanced or metastatic breast cancer with a PIK3CA mutation following progression on endocrine-based therapy. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 6 – 9 Jul 2026: The extension is based on Study CBYL719C2303 (C2303, EPIK-B5). Sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC were updated accordingly. [AI generated summary]

PRAC • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Clinical and molecular characterization of non-PIK3CA-related vascular malformations with overgrowth in a pediatric cohort. (PubMed, World J Pediatr) - "Non-PIK3CA VMs with overgrowth constitute a clinically and molecularly heterogeneous spectrum with substantial phenotypic overlap across genotypes, rendering phenotype-based classification unreliable. Somatic mosaicism, variable allele frequency, and tissue-specific expression underlie this heterogeneity. Our findings advocate for broad NGS panels with tissue-based analysis, systematic parental testing, and molecularly driven classification. The observed response to alpelisib in TEK-related disease supports the concept of convergent downstream pathway activation as a rationale for targeted therapies beyond PROS."

Journal • Pediatrics • EPHB4 • GNA11 • GNAQ • PIK3CA • PTEN • RASA1

CLAPO Syndrome: A Severe Case Revealed Prenatally and Treated With Alpelisib and Sclerotherapy (EADV 2026) - "Subsequent sclerotherapy with bleomycin and doxycycline resulted in a slow but progressive clinical improvement, allowing successful decannulation and recovery of spontaneous breathing...Sirolimus has shown partial efficacy in several congenital lymphatic malformations reported in the literature, but it was ineffective in our patient. Alpelisib, a selective PIK3CA inhibitor, has demonstrated promising results, including reductions in lesion size and symptom improvement. We report a severe CLAPO case showing improvement with combined alpelisib and sclerotherapy; however, its long-term efficacy and safety remain to be determined."

Clinical • Dyslipidemia • Infectious Disease • Respiratory Diseases • Severe Hypertriglyceridemia • PIK3CA

Phenotypic Heterogeneity within the PIK3CA-Related Overgrowth Spectrum: Three Pediatric Cases of MCAP, CLOVES Syndrome, and Klippel–Trenaunay Syndrome Managed with Multidisciplinary and Targeted Therapeutic Approaches (EADV 2026) - "With the emergence of targeted therapies such as sirolimus and alpelisib, early recognition and molecular characterization have become increasingly important. Concurrently, PDL therapy remained an important adjunctive modality for capillary malformation management. Early diagnosis through affected-tissue genetic sequencing, multidisciplinary collaboration, and individualized therapy are essential to optimize outcomes in patients with PIK3CA-related disorders."

Clinical • Heterogeneity • CNS Disorders • Developmental Disorders • Glaucoma • Hematological Disorders • Musculoskeletal Diseases • Ophthalmology • Pediatrics • Ventriculomegaly • PIK3CA

α-Chaconine as a Potential Inhibitor of Mutant Phosphatidylinositol 3-Kinase Alpha in Breast Cancer Stem Cells: Insights from Structure Prediction and Molecular Dynamics. (PubMed, Asian Pac J Cancer Prev) - "These findings provide a basis for further in vitro and in vivo studies to evaluate CHA as a selective PI3K inhibitor targeting the H1047R PIK3CA mutation in breast cancer stem cells."

Journal • Breast Cancer • Oncology • Solid Tumor • PIK3CA

PI3K inhibition with alpelisib and idelalisib enhances mIBG uptake in a preclinical neuroblastoma model (EANM 2026) - "We have previously demonstrated that administration of fimepinostat (CUDC-907), a dual histonedeacetylase and phosphoinositide 3-kinase (PI3K) inhibitor, enhances mIBG uptake both in vitro and in vivo in a NB xenograft mouse model.1 Since fimepinostat lacks regulatory approval, we investigated further clinically approved PI3K inhibitors to extend this strategy toward clinical translation. Both alpelisib and idelalisib significantly enhance [123I]mIBG tumour uptake in a NB xenograft, reinforcing PI3K inhibition as a viable strategy to improve mIBG-based theranostics. Idelalisib demonstrated the more favourable profile with consistent enhancement and low variability at the effective dose. Therapeutic studies combining these PI3K inhibitors with [131I]mIBG are underway to determine whether this ~40% increase in tumour uptake translates into improved treatment efficacy in the same preclinical model, with the aim of supporting future clinical translation."

Preclinical • Neuroblastoma • Solid Tumor • PIK3CA • PIK3CD

Improving public cancer care by implementing precision medicine in Norway (clinicaltrialsregister.eu) - P1/2 | N=1000 | Recruiting | Sponsor: Oslo University Hospital HF | N=6000 ➔ 1000

Enrollment change • Oncology

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Elacestrant (Ela) in combination with everolimus (Eve) or abemaciclib (Abema) in patients with ER+/HER2- locally advanced or metastatic breast cancer mBC: phase 2 results from ELEVATE, an open-label, umbrella study (AACR 2026) - "ELEVATE is evaluating Ela combined with Eve, alpelisib, capivasertib, Abema, ribociclib, or palbociclib to address resistance mechanisms. Ela combinations show a consistent clinically meaningful PFS irrespective of ESR1m status in pts with ER+/HER2- mBC after progressive disease on ET ± prior CDK4/6i, and could become an ET backbone for combination strategies, supporting an all-oral approach.NR, not reached *Maturity not reached for PFS (95% CI) for genomic subgroups (ESR1 / PIK3CA) or by prior CDK4/6i exposure."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Imlunestrant with or without everolimus or alpelisib, in ER+, HER2- advanced breast cancer (aBC): Results from the phase Ia/b EMBER study (ESMO 2023) - P1a/1b | "In the first-in-human phase 1a/b EMBER study, imlunestrant demonstrated favorable safety, pharmacokinetics (PK), and clinical benefit rate when administered as monotherapy (Jhaveri ASCO 2022) or with abemaciclib (Jhaveri SABCS 2022)...Median number of prior aBC therapies in combination cohorts was: 1 (range 1-2); including prior ET (100%), CDK4/6i (100%), fulvestrant (35%) and chemo (17%)...Conclusions Imlunestrant alone or in combination with everolimus or alpelisib demonstrated robust efficacy in pts with pre-treated ER+, HER-2 aBC. Toxicities were consistent with the known safety profile of both alpelisib and everolimus."

Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Comparative Efficacy of Second- and Later-Line BRAF-Targeted Regimens in BRAF V600E-Mutant Metastatic Colorectal Cancer: A Network Meta-Analysis (ACG 2026) - "Five trials enrolling 1,018 patients across eight treatment arms were included. All four experimental regimens demonstrated significant PFS benefit over irinotecan plus cetuximab. Encorafenib plus cetuximab plus alpelisib ranked highest for PFS (HR 0.29, 95% CI 0.19-0.47; P-score 0.923), followed by encorafenib plus binimetinib plus cetuximab (EBC; HR 0.38, 95% CI 0.29-0.49), encorafenib plus cetuximab (EC; HR 0.40, 95% CI 0.31-0.50), and vemurafenib plus irinotecan plus cetuximab (HR 0.48, 95% CI 0.32-0.72)."

Metastases • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study. (PubMed, J Clin Oncol) - "Imlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor activity in ER+/HER2- ABC."

Combination therapy • Journal • Metastases • Monotherapy • P1 data • Breast Cancer • Endometrial Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Exceptional response to alpelisib in a heavily pretreated patient with metastatic breast cancer carrying a PIK3CA mutation outside SOLAR-1 eligible mutations: a case report. (PubMed, Acta Oncol) - No abstract available

Journal • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PIK3CA

Advances in Management of Vascular Anomalies (ASH 2026) - "Because many of these genes are established oncogenes, cancer drugs have been repurposed for these conditions, exemplified by the PI3Kα inhibitor, alpelisib, now approved for PIK3CA-related overgrowth spectrum (PROS). Ricci synthesizes the genomic landscape across phenotypes and reviews the evidence for MEK, KRAS, and BRAF inhibition, with trametinib as the most established agent. This presentation then offers a genotype-guided framework for diagnosis and management, highlighting the expanding role of the hematologist-oncologist and the barriers to delivering equitable precision care."

CNS Disorders • Rare Diseases • AKT1 • KRAS • PIK3CA • PIK3R1 • PTEN

Research on the Role and Mechanism of Rehmannioside D in Regulating Fracture Healing. (PubMed, Curr Med Chem) - "RD promotes BMSC proliferation and osteogenic differentiation via activating the PI3K/AKT signaling pathway, accelerates callus remodeling and endochondral ossification, and ultimately improves femoral fracture healing in mice. RD is a promising natural active candidate for fracture repair intervention."

Journal • Musculoskeletal Diseases • Orthopedics • BMP2 • RUNX2

A Bleeding Ulcer That Wasn't: Gastric Metastasis From Invasive Ductal Breast Carcinoma (ACG 2026) - "Her oncologic course was marked by axillary nodal recurrence in 2017, followed by progressive metastatic disease involving lung, bone, liver, and brain, treated with anastrozole, letrozole, fulvestrant/everolimus, alpelisib, trastuzumab deruxtecan, and elacestrant. Gastroenterologists evaluating GI bleeding in patients with breast cancer history should pursue targeted biopsy with breast-directed immunohistochemistry, as accurate classification carries direct therapeutic implications. Figure: Endoscopic findings showing a 2.5 cm ulcer on the greater curvature of the proximal body and multiple additional ulcers up to 1.5 cm along the antrum, distal body, and proximal body of the stomach."

Breast Cancer • Gastric Cancer • Gastrointestinal Disorder • HER2 Positive Breast Cancer • Oncology • Peptic Ulcer • Solid Tumor • CDH1 • GATA3 • PGR

Single-Cell RNA Sequencing Reveals Immune Dysregulation and Candidate Drug Targets in Endometriosis. (PubMed, Cells) - "Computational drug repurposing analysis prioritized upadacitinib, sorafenib, alpelisib, and sulindac as hypothetical candidates for further investigation, with molecular docking identifying favorable predicted binding affinity scores, particularly for HSP90AA1. These results reinforce a systemic, immune-mediated view of endometriosis and nominate HSP90AA1 and PLCG2 as novel candidate targets that now require biochemical, chemical, and in vivo validation."

Journal • Endometriosis • Gynecology • Infertility • Inflammation • Pain • Sexual Disorders • Women's Health • CDC37 • HSP90AA1 • PLCG2

Investigating the impact of Sprouty-related EVH1 domain-containing protein 3 on gastric cancer prognosis and tumor microenvironments. (PubMed, Front Oncol) - "Immune infiltration was evaluated via CIBERSORT and TIDE algorithms, and drug sensitivity was predicted using GDSC database, with CETSA validating alpelisib-SPRED3 binding...Our results indicate that SPRED3 serves as a prognostic and immunological biomarker in gastric cancer. Conceptually, this study introduces SPRED3 as a previously unrecognized regulator in gastric cancer pathogenesis and immunity."

Biomarker • IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CD8 • PD-L1

INAVO121: Phase III study of inavolisib + fulvestrant vs alpelisib + fulvestrant in patients with hormone receptor-positive, HER2-negative, PIK3CA‑mutated locally advanced or metastatic breast cancer (SABCS 2023) - P3 | "Clinicaltrials.gov number NCT05646862. This abstract was originally presented at ASCO 2023 (TPS1123)."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial. (PubMed, J Clin Oncol) - "To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable."

Biomarker • IO biomarker • Journal • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • FGFR • PIK3CA

A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2). (ASCO 2026) - P3 | "Geda has superior preclinical potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus and demonstrated activity in PIK3CA-MT and wild-type (WT) breast cancer cell lines. These data demonstrate that gedatolisib combination therapies offer a potential new standard of care as 2L treatment of HR+/HER2- ABC, irrespective of PIK3CA mutation status."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

Assessing the pathogenic potential of PIK3CA gene variants in human cancer using a computational approach. (PubMed, J Biomol Struct Dyn) - "Structural modeling was performed to generate native and mutant p110α structures, followed by molecular docking to evaluate how these variants influence binding affinity with Alpelisib...However, the biological benefit or detriment of this shift warrants further experimental evaluation. The findings of this study may enhances our understanding of how PIK3CA variants contribute to predict disease risk and may support future precision-medicine approaches targeting the PI3K pathway."

Journal • Oncology • PIK3CA

Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. (PubMed, Cancer Cell) - "Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts."

Journal • Oncology • Ovarian Cancer • Solid Tumor