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Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3K alpha inhibitors
Neil Vasan
, Pedram Razavi
, Jared L. Johnson
, Hong Shao
, Hardik Shah
, Alesia Antoine
, Erik Ladewig
, Alexander Gorelick
,
Ting-Yu Lin
, Eneda Toska
, Guotai Xu
, Abiha Kazmi
, Matthew T. Chang
, Barry S. Taylor
, Maura N. Dickler
, Komal Jhaveri
, Sarat Chandarlapaty
, Raul Rabadan
, Ed Reznik
, Melissa L. Smith
Robert Sebra, Frauke Schimmoller, Timothy R. Wilson, Lori S. Friedman, Lewis C. Cantley, Maurizio Scaltriti, Jose Baselga
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Biochemistry, Genetics and Molecular Biology
Clinical Trial
100%
Lipid
100%
Cancer Cell
100%
Phosphotransferase
100%
Kinase
100%
Oncogene
100%
Single Molecule Real Time Sequencing
100%
Prevalence
50%
Amino Acids
50%
Enzyme Active Site
50%
Signal Transduction
50%
Tumor Progression
50%
Codon
50%
Next Generation Sequencing
50%
Cell Viability
50%
Mammalian Target of Rapamycin
50%
Cell Mutant
50%
Circulating Tumor DNA
50%
Biochemical Mechanism
50%
Randomized Clinical Trial
50%
Genomics
50%
Fulvestrant
50%
Keyphrases
In Cis
100%
Phosphoinositide 3-kinase (PI3K)
100%
Oncogenicity
100%
Alpha Inhibitors
100%
PIK3CA mutation
100%
PI3K Inhibitor
50%
Tumor
44%
Breast Cancer
27%
Alpelisib
27%
Double mutation
22%
ER +
22%
Taselisib
22%
Placebo
16%
Double mutant
16%
PIK3CA
16%
Objective Response Rate
16%
P110
16%
Kinase Activity
11%
Primary Tumor
11%
Metastatic Breast Cancer
11%
Metastatic Tumor
11%
Single-molecule Sequencing
11%
Single-point mutation
11%
Clinical Benefit
11%
ER+ Breast Cancer
11%
Cancer Histology
11%
H1047R
11%
PI3K Pathway
11%
Multiple mutants
11%
Nave
5%
Lipids
5%
Cell Growth
5%
Breast Tumor
5%
Human Cancer
5%
Response Data
5%
Phosphorylation
5%
Cell Viability
5%
Grade Level
5%
Cancer Therapy
5%
Breast Cancer Patients
5%
Oncogene
5%
Clinically Significant
5%
Recombinant
5%
Codon
5%
Lipid Binding
5%
Targeted Therapy
5%
FDA-approved Drugs
5%
Amino Acid Position
5%
Mammalian Target of Rapamycin (mTOR)
5%
Signaling Cascades
5%
Signaling Complex
5%
Genetic Modification
5%
Pathway Inhibitors
5%
Downstream Signaling
5%
Mutant Cells
5%
Tumor Histology
5%
Cell Tumor
5%
Cell Signaling
5%
All Cancer
5%
Response Predictors
5%
Number of Patients
5%
Proliferation in Vitro
5%
Tumor Samples
5%
Standard of Care
5%
Catalytic Subunit
5%
Non-oncogene Addiction
5%
Multiple Cancers
5%
Circulating Tumor DNA (ctDNA)
5%
Multiple mutations
5%
Biochemical Mechanism
5%
Degrader
5%
Regulatory Subunit
5%
Enrichment Analysis
5%
Biological Relevance
5%
Disrupter
5%
Pathway Signaling
5%
Tumor Proliferation
5%
Differential Sensitivity
5%
HER2 Breast Cancer
5%
Independent Primary
5%
Phase III Clinical Trial
5%
Oncogenic mutations
5%
Phosphotyrosine
5%
Phosphatidylinositol 4,5-bisphosphate (PIP2)
5%
Randomized Clinical Trial
5%
Early Phase Clinical Trials
5%
Catalytic Inhibition
5%
Fulvestrant
5%
PIP3
5%
Biological Correlation
5%
RTK Signaling
5%
Allelic Configuration
5%
Medicine and Dentistry
Breast Cancer
100%
Carcinogenicity
100%
Neoplasm
88%
Arm
66%
Alpelisib
55%
Taselisib
44%
Placebo
33%
Clinical Trial
22%
Metastatic Carcinoma
22%
Primary Tumor
22%
Cancer Cell
22%
Phosphotransferase
22%
Single Molecule Real Time Sequencing
22%
Metastatic Breast Cancer
22%
Prevalence
11%
In Vitro
11%
Malignant Neoplasm
11%
Tumor Progression
11%
Cancer
11%
Signal Transduction
11%
Targeted Therapy
11%
Cancer Therapy
11%
Cell Viability
11%
Breast Tumor
11%
Cell Mutant
11%
Amino Acid
11%
Codon
11%
Oncogene
11%
Next Generation Sequencing
11%
Randomized Clinical Trial
11%
Mammalian Target of Rapamycin
11%
Proteus Syndrome
11%
Tumor Histology
11%
Enzyme Active Site
11%
Oncogene Addiction
11%
Fulvestrant
11%
Phosphotyrosine
11%
Cell Signaling Pathway
11%
Pharmacology, Toxicology and Pharmaceutical Science
Breast Cancer
100%
Neoplasm
100%
Carcinogenicity
100%
Alpelisib
55%
Taselisib
44%
Placebo
33%
Malignant Neoplasm
22%
Clinical Trial
22%
Metastasis
22%
Primary Tumor
22%
Phosphotransferase
22%
Metastatic Breast Cancer
22%
Prevalence
11%
Amino Acid
11%
Tumor Growth
11%
Cell Viability
11%
Breast Tumor
11%
Multiple Cancer
11%
Randomized Clinical Trial
11%
Phosphotyrosine
11%
Oncogene Addiction
11%
Fulvestrant
11%
Immunology and Microbiology
Arm
100%
P110δ
50%
Cancer Cell
33%
Oncogene
33%
Prevalence
16%
Signal Transduction
16%
Codon
16%
Tumor Cell
16%
Enzyme Active Site
16%
Cell Viability
16%
Next Generation Sequencing
16%
Cell Mutant
16%
Amino Acid
16%