liquid biopsy, present and future -...
TRANSCRIPT
Liquid Biopsy, present and future
LAURA MUINELO ROMAY,
LIQUID BIOPSY ANALYSIS UNIT,
ONCOMET, IDIS, SANTIAGO DE COMPOSTELA
SANTANDER 13-7-2017
Liquid Biopsy
Siravenga et al., Nature Rev 2017
What are we looking for?
Liquid Biopsy advantages
Stephen Paget, 1889
•T.R. Ashworth,
Austrian
Medical
Journal, 14:
146, 1869.
PAST
Circulating tumour cells (CTCs)
PAST
Cell-free DNA (cfDNA)
PAST
https://linknovate.com
PRESENT
Technology
- The low number
Marusyk et al. Nature Reviews Cancer (2012)
-The tumour heterogeneity
We need versatile techniques
CTCs PRESENT
Miyamoto el al. Nature Reviews Clinical Oncology 11, 401–412 (2014)
CTCs PRESENT
Technology
< 40 devices for CTCs isolation commercialized
CTCs PRESENT
Molecular characterization of CTCs
Yu et al., J. Cell Biol 2011
CTCs PRESENT
CTCs PRESENT
Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients
Arun et al Scientific Rep, 2016
CTCs PRESENT
CTCs in vitro/ ex vivo expansion
CTCs PRESENT
Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility
CTCs ex vivo expansion
Yu et al. Science 2014
CTCs PRESENT
Yu et al. Science 2014
Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility
CTCs PRESENT
CTCs PRESENT
CTCs PRESENT/CLINICAL VALIDATION
CellSearch system
-The unique system FDA clearance to be applied with clinical objectives for metastasic breast, prostate and colon cancer
Semi-automatic Highly reproducible -Only EpCAM and CK positive cells -Limited for downtream analyses
Cabel et al., Int J Clin Oncol, 2017
CTCs PRESENT/CLINICAL VALIDATION
Technical limitations for ctDNA studies
ctDNA may come from primary tumors, metastatic lesions, or CTCs
The fraction of ctDNA is normally less than 0.1%
cfDNA in the circulation is typically fragmented to 160 to 180 bp in length
ctDNA PRESENT
Wan et al. Nat Rev Cancer 17 (4), 223-
238. 2017
How we can analyze ctDNA ???
Bronte, et al. New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do
all roads lead to RAS? Oncotarget. 2015 Sep 22;6(28):24780-96.
ctDNA PRESENT
Terascreen
• First companion diagnostic kit based on liquid biopsies • 29 EGFR mutations; • Sensitivity: 65.7%; Specifity: 99.8%
• 42 mutaciones en EGFR • Sensibilidad por mutaciones activadoras: 82% • Especificidad: 98%
COBAS (ROCHE)
ctDNA PRESENT
Idylla (Biocartis)
ctDNA PRESENT
ctDNA PRESENT
ctDNA PRESENT
Calabuig-Fariñas et al.,Transl Lung Cancer Res. 2016
FUTURE
Technological development and validation
Liquid biopsy based tests
Must be: • High sensitive/specifity • Repeatable • rapid • cost-effective • compatible with process
automation
FUTURE
FUTURE
LIQUID BIOPSY TECHNOLOGICAL REVOLUTION AND FIGHT
Global Liquid Biopsy Market was valued at $634 million in 2016, and is estimated to reach at $3,805 million by 2023
FUTURE
Clinical validation
Early Detection and Genotyping of Solid Tumors: in Blood Veritas?
Can Liquid Biopsy Detect and Monitor Minimal Residual Disease in Early-Stage Patients?
Can We Use Liquid Biopsy to Guide Therapy? In which tumours?
When we have to perform the analysis? Which cutoffs we have to use?
Could we use Liquid biopsy for cancer screening?
FUTURE
Clinical validation
Clinical utility requires that the use of a liquid biopsy test demonstrate the added
benefit of patient management and treatment decision-making
TOTAL 2876 Completed 1235 Active 1328
CLINICAL TRIALS INCLUDING CTCs
FUTURE
https://clinicaltrials.gov/
TOTAL 277 Completed 45 Active 205
CLINICAL TRIALS INCLUDING ctDNA
FUTURE
https://clinicaltrials.gov/
CLINICAL TRIALS INCLUDING ctDNA IN USA
FUTURE
https://clinicaltrials.gov/
Liquid biopsy analysis will provide a large amount of data that we need
to intepret together with clinical parameters to reach
PRECISION ONCOLOGY
Liquid biopsy heating up, but is it a big data problem?
FUTURE
CONCLUSION
Nowadays we have a broad spectrum of technologies with proved high sensitivity and specifity to analyse liquid biopsies however there is an important need of standarization and consensus regarding which technique should be used in each clinical context Although applications of liquid biopsies in oncology have emerged and developed at an incredible rate over the past 5 years implementation of liquid biopsy approaches in clinical practice will occur only after extensive controlled studies are performed.
There is a NEW ERA in Oncology and we have to go FAST but SAFE to give patients more
personalyzed treatments
PRESENT/FUTURE OF LIQUID BIOPSY
Dr. Soria "I really think ― and I'm ready to bet ― that this is the most transformational thing that's going to happen in oncology in terms of how it's going to impact cancer clinical trials and cancer daily management for the next 5 years."
“This could change forever the way we follow up not only response to treatments but also the emergence of resistance, and down the line could even be used for really early diagnosis”
Dr. Baselga
GRACIÑAS¡¡
YA VEREMOS
ES LA LECHE ESTO DE LA BIOPSIA LÍQUIDA¡¡
Technological development and validation
FUTURE
Siravenga et al., Nature Rev 2017
CTCs PRESENT
Novello et al Metastatic Non-Small-Cell Lung Cancer: ESMO Clinical Practice Guidelines Annal Oncol 2016