Curcumin alone led to dose-dependent responses and when combined with BYL719, positive effects were revealed, as they were when it was combined with MK-1775 or PD-0332991, suggesting a potential use of some of these combinations for HPV+ OPSCC.

1 day ago

Preclinical • Journal • PARP Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • CDK4 (Cyclin-dependent kinase 4) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CDC27 (Cell Division Cycle 27)

PIK3CA mutation

cisplatin • Ibrance (palbociclib) • Talzenna (talazoparib) • Piqray (alpelisib) • Balversa (erdafitinib) • adavosertib (AZD1775)

Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation. (PubMed, J Clin Med)

Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

2 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases. (PubMed, J Pers Med)

These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

3 days ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein)

HER-2 positive • TP53 mutation • PIK3CA mutation • PTEN mutation • ATR mutation • CHEK2 mutation

AutoEpiCollect, a Novel Machine Learning-Based GUI Software for Vaccine Design: Application to Pan-Cancer Vaccine Design Targeting PIK3CA Neoantigens. (PubMed, Bioengineering (Basel))

Future studies could aim to validate AutoEpiCollect's vaccine design in murine models affected by PIK3CA-mutated or other mutated tumor cells located in various tissue types. AutoEpiCollect streamlines the preclinical vaccine development process, saving time for thorough testing of vaccinations in experimental trials.

3 days ago

Journal • Pan tumor • Machine learning

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line. (PubMed, Curr Issues Mol Biol)

We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

3 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • IL6 (Interleukin 6)

KRAS mutation • PIK3CA mutation • PGR expression • PIK3CA mutation + KRAS mutation

Mutant RAS-driven secretome causes skeletal muscle defects in breast cancer. (PubMed, Cancer Res Commun)

Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Since RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects.

6 days ago

Journal • BRCA Biomarker

ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • RAS (Rat Sarcoma Virus) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • MIR486-1 (MicroRNA 486-1) • PAX7 (Paired Box 7)

BRCA2 mutation • ER positive • PIK3CA mutation • PIK3CA H1047R • RAS mutation • HRAS mutation • PGR positive • NRAS G12 • HRAS G12V

Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project. (PubMed, JCO Precis Oncol)

We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.

7 days ago

Journal • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • GATA3 (GATA binding protein 3)

HR positive • HER-2 negative • PIK3CA mutation • ESR1 mutation • EGFR positive

Verzenio (abemaciclib)

Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. (PubMed, Proc Natl Acad Sci U S A)

However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

9 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • PVT1 (Pvt1 Oncogene) • RPL10 (Ribosomal Protein L10)

KRAS mutation • PIK3CA mutation • ARID1A mutation • KMT2D mutation

Gilotrif (afatinib) • Aliqopa (copanlisib) • elimusertib (BAY 1895344)

10d

Celecoxib and sulindac sulfide elicit anticancer effects on PIK3CA-mutated head and neck cancer cells through endoplasmic reticulum stress, reactive oxygen species, and mitochondrial dysfunction. (PubMed, Biochem Pharmacol)

Gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Salubrinal and N-acetyl-L-cysteine attenuated celecoxib-induced mitochondrial dysfunction. Collectively, our results suggest that celecoxib and SUS efficiently suppress activating PIK3CA mutation-harboring HNC progression by inducing ER and oxidative stress and mitochondrial dysfunction, leading to apoptotic cell death, further supporting NSAID treatment as a useful strategy for oncogenic PIK3CA-mutated HNC therapy.

10 days ago

Journal • IO biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2L11 (BCL2 Like 11) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • ATF4 (Activating Transcription Factor 4) • TNFRSF10B (TNF Receptor Superfamily Member 10b) • TCF4 (Transcription Factor 4)

PIK3CA mutation • PIK3CA H1047R • CASP3 elevation

salubrinal • celecoxib oral

11d

Preventing alpelisib-related hyperglycaemia in HR+/HER2-/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial. (PubMed, EClinicalMedicine)

In HR+/HER2-/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia. Novartis Pharmaceuticals.

11 days ago

P2 data • Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

Piqray (alpelisib) • metformin

12d

TPST-1495-001: Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors (clinicaltrials.gov)

P1, N=175, Active, not recruiting, Tempest Therapeutics | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial primary completion date: Apr 2024 --> Sep 2024

12 days ago

Enrollment closed • Phase classification • Trial primary completion date • Combination therapy

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

Keytruda (pembrolizumab) • TPST-1495

12d

STX-478-101: First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=400, Recruiting, Scorpion Therapeutics, Inc. | Trial completion date: Apr 2028 --> Feb 2029 | Trial primary completion date: Apr 2026 --> Feb 2027

12 days ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

fulvestrant • STX-478

12d

Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven Non-Small-Cell-Lung-Cancer with PIK3CA/PTEN alterations. (PubMed, Clin Cancer Res)

Together, this approach offers a potential treatment strategy for patients with EGFRm-driven NSCLC that have a sub-optimal response, or develop resistance, to osimertinib through PIK3CA/AKT/PTEN alterations.

12 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)

EGFR mutation • PIK3CA mutation • PTEN mutation • EGFR mutation + PTEN mutation

Tagrisso (osimertinib) • Truqap (capivasertib)

13d

Prevalence and Associations of Co-occurrence of NFE2L2 Mutations and Chromosome 3q26 Amplification in Lung Cancer. (PubMed, Glob Med Genet)

Conclusions NFE2L2 mutations display notable heterogeneity in lung cancer. The coexistence of NFE2L2 mutations and 3q26 amplification warrants in-depth exploration of their potential clinical implications and treatment approaches for affected patients.

13 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • LRP1B (LDL Receptor Related Protein 1B) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • SOX2 • KMT2B (Lysine Methyltransferase 2B) • IRF2 (Interferon Regulatory Factor 2) • ZMAT3 (Zinc Finger Matrin-Type 3)

PIK3CA mutation • NFE2L2 mutation

14d

Correlation between NGS panel-based mutation results and clinical information in colorectal cancer patients. (PubMed, Heliyon)

Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

14 days ago

Journal • Next-generation sequencing • MSi-H Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway)

TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • PIK3CA mutation • TP53 wild-type • APC mutation • SMAD4 mutation

15d

Understanding PI3K/Akt/mTOR signaling in squamous cell carcinoma: mutated PIK3CA as an example. (PubMed, Mol Biomed)

However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.

15 days ago

Review • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • PIK3CA E542K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L

16d

Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling. (PubMed, Cell Rep Med)

Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

16 days ago

Journal • Tumor cell

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

PIK3CA mutation

Piqray (alpelisib) • VTP-50469

16d

The Molecular Landscape of Gastric Cancers for Novel Targeted Therapies from Real-World Genomic Profiling. (PubMed, Target Oncol)

Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.

16 days ago

Journal • Real-world evidence • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • CDH1 (Cadherin 1)

BRAF V600E • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET amplification • MET mutation • KRAS G12

18d

Comprehensive characterization of genomic features and clinical outcomes following targeted therapy and secondary cytoreductive surgery in OCCC: a single center experience. (PubMed, J Gynecol Oncol)

Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

18 days ago

Clinical data • Journal • Tumor mutational burden • IO biomarker • Surgery

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • ARID1A (AT-rich interaction domain 1A) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

KRAS mutation • PIK3CA mutation • ARID1A mutation • FGFR2 mutation • NBN mutation

Avastin (bevacizumab)

18d

Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)

P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2028 --> May 2028

18 days ago

Trial completion date • Trial initiation date • Trial primary completion date

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)

PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation

everolimus • Kisqali (ribociclib)

18d

Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer. (PubMed, Surg Oncol)

We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in clinical practice.

18 days ago

Journal • Circulating tumor DNA • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

19d

Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children's Oncology Group Study. (PubMed, Neurooncol Adv)

Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.

19 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • TERT (Telomerase Reverse Transcriptase) • TERC (Telomerase RNA Component)

PIK3CA mutation • PTEN mutation

Avastin (bevacizumab) • temozolomide • Zolinza (vorinostat)

20d

Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer. (PubMed, Sci Rep)

Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

20 days ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • BRCA (Breast cancer early onset)

PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • PD-L1 underexpression • ARID1A mutation • BRCA wild-type • TP53 expression • BRCA mutation • HER-2 amplification + PD-L1 expression • PD-L1-L

20d

Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer (ALPHABET) (clinicaltrials.gov)

P3, N=27, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=300 --> 27 | Trial completion date: Sep 2026 --> Nov 2024 | Trial primary completion date: Jun 2026 --> Nov 2024

20 days ago

Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)

ER positive • PIK3CA mutation • PGR expression

Herceptin (trastuzumab) • capecitabine • Piqray (alpelisib) • fulvestrant • Halaven (eribulin mesylate) • vinorelbine tartrate • Navelbine oral (vinorelbine tartrate oral)

21d

Gastric carcinoma in autoimmune gastritis: a histopathologic and molecular study. (PubMed, Mod Pathol)

The most frequently altered genes were: TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [two amplified and five mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with long-standing misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB-high.

21 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • CLDN18 (Claudin 18) • MUC1 (Mucin 1) • RNF43 (Ring Finger Protein 43) • CDX2 (Caudal Type Homeobox 2) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)

TMB-H • HER-2 amplification • PIK3CA mutation • HER-2 mutation • ARID1A mutation

22d

Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I) (clinicaltrials.gov)

P2, N=70, Active, not recruiting, National Cancer Institute (NCI)

22 days ago

Trial completion date

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

taselisib (GDC-0032)

22d

Trametinib and Trifluridine and Tipiracil Hydrochloride in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery (clinicaltrials.gov)

P1, N=26, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023

22 days ago

Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Surgery • Metastases

BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)

BRAF mutation • PIK3CA mutation • BRAF wild-type • RAS mutation • RAS wild-type • RAS wild-type + BRAF wild-type • PIK3CA mutation + PTEN mutation

Mekinist (trametinib) • Lonsurf (trifluridine/tipiracil)

22d

Body composition measures as a determinant of Alpelisib related toxicity. (PubMed, Breast Cancer Res Treat)

Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

22 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

Piqray (alpelisib)

23d

Cryo-EM structures reveal two allosteric inhibition modes of PI3KαH1047R involving a re-shaping of the activation loop. (PubMed, Structure)

Structural and MD simulation analyses show that the allosteric binding of QR-7909 and QR-8557 inhibit PI3KαH1047R hyper-activity by reducing the fluctuation and mobility of the activation loop. Our work provides a strong rational basis for a further optimization and development of highly selective drug candidates to treat PI3KαH1047R-driven cancers.

23 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation • PIK3CA H1047R

23d

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer. (PubMed, Cancer Discov)

TAN-High tumours harboured recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis.

23 days ago

Clinical data • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

23d

The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features. (PubMed, J Pathol Clin Res)

Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.

23 days ago

Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

ER positive • HER-2 negative • PIK3CA mutation • PTEN expression • AKT1 mutation • MTOR mutation

everolimus

25d

Synergistic effects of the combination of trametinib and alpelisib in anaplastic thyroid cancer with BRAF and PI3KCA co-mutations. (PubMed, Heliyon)

Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAFV600E mutation. The combination of trametinib and alpelisib showed promise as a strategy for treating ATC with co-mutations in BRAF and PI3KCA, both in vitro and in vivo. This combination offers insights into overcoming resistance to BRAF-targeted treatments in ATC with mutations in BRAF and PI3KCA.

25 days ago

Journal

BRAF (B-raf proto-oncogene)

BRAF V600E • BRAF mutation • PIK3CA mutation • BRAF V600

Mekinist (trametinib) • Tafinlar (dabrafenib) • Piqray (alpelisib)

25d

Prognostic and predictive biomarkers with therapeutic targets in nonsmall-cell lung cancer: A 2023 update on current development, evidence, and recommendation. (PubMed, J Oncol Pharm Pract)

Advances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.

25 days ago

Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • BRAF V600 • EGFR exon 20 insertion • RET mutation • MET mutation • KRAS G12 • EGFR exon 20 mutation

25d

Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA. (PubMed, Hum Cell)

Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.

25 days ago

Preclinical • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)

PIK3CA mutation • ARID1A mutation • PIK3CB mutation

27d

Capivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer. (PubMed, Ann Pharmacother)

In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy. Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.

27 days ago

Review • Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)

HR positive • HER-2 negative • PIK3CA mutation • PTEN mutation • AKT1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive

fulvestrant • Truqap (capivasertib)

28d

Optimal targeting of PI3K-AKT and mTOR in advanced oestrogen receptor-positive breast cancer. (PubMed, Lancet Oncol)

Approvals for oestrogen receptor-positive advanced breast cancer include the PI3K inhibitor alpelisib for PIK3CA-mutated tumours, the AKT inhibitor capivasertib for tumours with alterations in PIK3CA, AKT1, or PTEN, and the mTOR inhibitor everolimus, which is used irrespective of mutation status. The availability of different inhibitors leaves physicians with a potentially challenging decision over which of these therapies should be used for individual patients and when. In this Review, we present a comprehensive summary of our current understanding of the pathways and the three inhibitors and discuss strategies for the optimal sequencing of therapies in the clinic, particularly after progression on a CDK4/6 inhibitor.

28 days ago

Review • Journal • Metastases

ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

ER positive • PIK3CA mutation • PTEN mutation

everolimus • Piqray (alpelisib) • Truqap (capivasertib)

28d

Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study. (PubMed, Lancet Oncol)

Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile.

28 days ago

P1 data • Journal • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • PTEN mutation + HR positive

Ibrance (palbociclib) • fulvestrant • letrozole • gedatolisib (PF-05212384)

Pathologic Features of Brain Hemorrhage After Radiation Treatment: Case Series with Somatic Mutation Analysis. (PubMed, J Stroke Cerebrovasc Dis)

Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

1 month ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CD163 (CD163 Molecule) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)

PIK3CA mutation • PTEN mutation

GO39374: To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer (clinicaltrials.gov)

P1, N=256, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

1 month ago

Enrollment closed • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HER-2 negative • PIK3CA mutation

Herceptin (trastuzumab) • Ibrance (palbociclib) • Perjeta (pertuzumab) • fulvestrant • letrozole • metformin • inavolisib (GDC-0077)

Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. (PubMed, Clin Cancer Res)

sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

1 month ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 mutation • HRD • MYC amplification • CCNE1 amplification • HRD + BRCA1 mutation • HRD signature

Cold Tumour Phenotype Explained Through Whole Genome Sequencing in Clinical Nasopharyngeal Cancer: A Preliminary Study. (PubMed, Immunotargets Ther)

Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.

1 month ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)

PIK3CA mutation

Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity. (PubMed, Gynecol Oncol)

Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.

1 month ago

Journal • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • PIK3CA E545

Piqray (alpelisib)