Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis:...
Transcript of Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis:...
![Page 1: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/1.jpg)
Personalized Cancer Therapy (a cohort of one)
Brent Zanke MD PhD FRCPC
![Page 2: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/2.jpg)
Provincial Cancer Care Conference 2018
Presenter Disclosure
•Faculty/Speaker: Brent Zanke
•Relationships with financial sponsors: –Grants/Research Support: None.
–Speakers Bureau/Honoraria: None
–Consulting Fees: None
–Other: Chief Medical Officer, Chairman and Founder of ArcticDx Inc.
![Page 3: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/3.jpg)
Learning Objectives
• To understand existing approaches to personalizing cancer therapy
• To learn about new approaches to cancer pharmacogenomics including liquid biopsy and NextGen sequencing.
Provincial Cancer Care Conference 2018
![Page 4: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/4.jpg)
Personalized therapy
![Page 5: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/5.jpg)
Radical
Treatment
Active
Surveillance
Bx
Current Prostate Cancer Personalized Therapy
![Page 6: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/6.jpg)
Personalized medicine: genetic/proteomic biomarkers distinguish predisposition/response/toxicity
![Page 7: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/7.jpg)
Cancer arises from DNA mutations in cells
![Page 8: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/8.jpg)
Genetic markers can predict individual sensitivity to lung cancer treatment.
![Page 9: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/9.jpg)
Lung Cancer Genetic Variability affects TKI
sensitivity Epidermal Growth Factor Receptor (EGFR)
Most common sensitizing mutations: exon 19 deletion or L858R point mutation in exon 21
![Page 10: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/10.jpg)
Other important mutations
• ALK (Anaplastic Lymphoma Kinase) – sensitivity to TKI Crizotinib
• ROS1 – RTK – fusion mutations = responsiveness to oral ROS1 TKI
• BRAF S/T Kinase – V600E associated with responsiveness to combination therapy with oral inhibitors
of BRAF and MEK
• KRAS. Activating mutations in codon 12 : reduced responsiveness to EGFR TKI
• PD-L1 expression determines sensitivity to check point inhibitors
Non-Small Cell Lung Cancer Genetic Testing and Drug Sensitivity
![Page 11: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/11.jpg)
Breast Cancer: Can good prognosis Stage 1, HR+, Her2neg
adjuvant candidates be saved adjuvant chemotherapy? A personalized approach.
![Page 12: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/12.jpg)
OncotypeDx
![Page 13: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/13.jpg)
![Page 14: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/14.jpg)
JCO 2006
OncotypeDX score for node negative ER+ tumors (NSABP 20)
![Page 15: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/15.jpg)
The future of personalized cancer treatment
![Page 16: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/16.jpg)
The Problem
Diagnosis: Invasive Tumor Biopsy
• Tumor biopsies are costly, painful and
can result in complications.
The Proposed Solution
Diagnosis: Non-Invasive Liquid Biopsy
16 Liquid biopsy is less invasive than needle biopsy
![Page 17: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/17.jpg)
![Page 18: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/18.jpg)
![Page 19: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/19.jpg)
![Page 20: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/20.jpg)
Your DNA may not be the only thing personal about you!
Bacterial diversity can affect efficacy of cancer treatment
![Page 21: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/21.jpg)
Response to PD-1 blockage in metastatic melanoma as a function of fecal diversity.
![Page 22: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/22.jpg)
Fecal transplant: A new frontier in personalized medicine
Drug sensitivity influenced by gut bacterial composition
![Page 23: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/23.jpg)
An increasingly important management partner
![Page 24: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/24.jpg)
NextGen Sequencing $1000 genome
![Page 25: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/25.jpg)
Tumor whole genome sequencing to select treatment
![Page 26: Personalized Cancer Therapy · The future of personalized cancer treatment . The Problem Diagnosis: Invasive Tumor Biopsy • Tumor biopsies are costly, painful and can result in](https://reader034.fdocuments.net/reader034/viewer/2022042806/5f6d9772df5e7040d6080905/html5/thumbnails/26.jpg)
• Sequencing technologies are becoming inexpensive • Big data and artificial intelligence are resolving
complexity into order • Less invasive techniques are evolving to allow frequent
sampling and personalized treatment selection. • This will result in better outcomes and (?) less
expensive care.
Summary