9:00 am Coffee & Networking

10:00 am Chair’s Opening Remarks

10:00 am Exploring the Impact of Diet & Elevated Insulin

  • Lewis Cantley Director, Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital

Synopsis

• Explore the evolution of PI3K alpha from orthologs in flies and worms that mediate growth in response to insulin. In humans, other growth factors such as PDGF and EGF can activate PI3K alpha.
• Investigate the implication of activating mutations in PIK3CA and loss of function mutations or deletions in PTEN in human cancers
• Evaluate the impact of acute insulin resistance caused by multiple PI3K alpha inhibitors and the mechanism by which high levels of serum insulin can compromise the effects of these drugs
• Discover the potential of interventions that lower serum insulin, including sodium-glucose co transporter inhibitors that block reabsorption of glucose in the kidney, and low carbohydrate diets that reduce glucose influx from the digestive system, to increase responses to PI3Kα inhibitors in mouse preclinical models of cancers

10:30 am Profiling Lipid Kinase Inhibitors on KiNativ® – Confirming On-target Potency & Selectivity in Therapeutically Relevant Tissue

Synopsis

  • Selectivity profiling against native kinases (full-length kinases in the presence of cellular binding partners) in samples derived from any species
  • Covers more lipid kinases than other platforms that offer orthogonal profiling services
  • Allows determination of target engagement in treated animals, including human

10:45 am Harnessing the Metabolism of PI3K Signaling for More Effective Anti-Cancer Therapy

  • George Poulogiannis Team Leader, Signaling & Cancer Metabolism, The Institute of Cancer Research

Synopsis

• Metabolic fingerprinting can assist with the diagnosis and therapy decision-making of PIK3CA mutant cancers
• PI3K/AKT activation drives the overproduction of bio-active lipids to support cell proliferation and migration beyond a cell-autonomous manner
• Diet boosts the effectiveness of targeted therapies in PIK3CA-induced tumorigenesis

11:15 am Beyond Hematological Malignancies: the Case for PI3K Inhibition in Brain Cancer

  • James Garner Chief Executive Officer & Managing Director, Kazia Therapeutics

Synopsis

• Relevance of the PI3K pathway to primary and secondary brain cancers
• Opportunities and challenges in the application of PI3K inhibitors to brain cancer Paxalisib – a novel PI3K / mTOR inhibitor in development for glioblastoma

11:45 am Morning Refreshments & Networking

Targeting AKT/PI3K/MTOR Pathway and Potential Therapies

12:15 pm PI3Kinase Inhibition in Head and Neck Cancer

  • Jochen Lorch Professor of Medicine & Medical Director of the Head & Neck Program , Northwestern University

Synopsis

• Explore past challenges with PI3K inhibition in treating head and neck cancer
• Gain and update on current strategies and uses of PI3K inhibition in treating head and neck cancer
• Delve into promising future developments

12:45 pm Genomic Alteration of the PI3K/AKT/MTOR Pathway: a Pan- Cancer Perspective

  • Philip Beer Visiting Scientist , Wellcome Trust Sanger Institute

Synopsis

• Mutations in PIK3CA, PTEN and AKT1 occur in many different cancer types, opening the door for expanded indications for targeted therapies
• Genomic analysis can identify tumor types where responses to targeted therapy are more or less likely to work, based on co-existing mutations
• A long tail of rarer mutations in other pathway components identifies additional therapeutic opportunities

1:15 pm AKT Signaling Pathways & the Therapeutic Potential of AKT Inhibitors in Oncology

  • Igor Vivanco Senior Lecturer, Institute of Cancer Research

Synopsis

• Current state of AKT inhibitor development.
• Single agent activity vs combinations: how to choose the right combo and the right patients.
• Non-catalytic functions of AKT and their impact on how we do drug development

1:45 pm Lunch & Networking

Exploring Implications of PI3K in Disorders Outside of Oncology

2:45 pm Activated PI3Kδ Syndrome (APDS) is an Inborn Error of Immunity Caused by Activating Mutations in PIK3CD (APDS1) or PIK3R1 (APDS2)

Synopsis

• Investigate the causes and symptoms of APDS including increased susceptibility to infections leading to pneumonia and chronic lung disease and high risk of lymphoproliferative disease and B cell lymphoma
• Explore the response of APDS patients to PI3Kδ inhibitor, Leniolisib, including mouse model data recapitulating disease features

3:15 pm A Pre-Clinical Cancer Prevention Trial Using PI3K Pathway Inhibitors in a Mouse Model for PTEN Hamartoma Syndrome (PHTS)

Synopsis

• PTEN Hamartoma Syndrome (PHTS) is rare disease caused due to heterozygous germline PTEN mutations
• PHTS patients have an increased risk of cancers of the thyroid, breast, endometrium, colon and melanomas
• Repurposing PI3K inhibitors and inhibitors of PI3 Kinase pathway components such as AKT and mTOR for treatment of PHTS
• Data from a pre-clinical study on cancer prevention using some of these inhibitors in a PHTS mouse model

3:45 pm Activated PI3Kdelta Syndrome – A Novel Combined Immunodeficiency

  • Anita Chandra Consultant Clinical Immunologist, Addenbrooke's Hospital Associate Principal Investigator at the Department of Medicine, University of Cambridge

Synopsis

• In this presentation I will provide a clinical description of this novel
immunodeficiency
• Discuss the mechanism of the underlying immunodeficiency
• Discuss the various treatment options available to the patients including
selective PI3K delta inhibitors.

4:15 pm Chair’s Closing Remarks

4:30 pm Close of Summit