Liquid Biopsy, Present and Future

Liquid Biopsy, Present and Future

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Description: Concordance of Anaplastic Lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in one-small cell lung cancer. Potential role nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients. Clinical significance of Androgen Receptor Splice variant-7 mRNA Detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first and second line abiraterone and enzalutamide.

 
Author: Laura Muinelo Romay  | Visits: 216 | Page Views: 454
Domain:  Medicine Category: Therapy 
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Contents:
Liquid Biopsy, present and future
LAURA MUINELO ROMAY,
LIQUID BIOPSY ANALYSIS UNIT,
ONCOMET, IDIS, SANTIAGO DE COMPOSTELA
SANTANDER 13-7-2017

Liquid Biopsy

What are we looking for?

Siravenga et al., Nature Rev 2017

Liquid Biopsy advantages

PAST
Circulating tumour cells (CTCs)

•T.R. Ashworth,
Austrian
Medical
Journal, 14:
146, 1869.

Stephen Paget, 1889

PAST

Cell-free DNA (cfDNA)

PAST

https://linknovate.com

PRESENT

CTCs PRESENT
Technology
- The low number

-The tumour heterogeneity

We need versatile techniques

Marusyk et al. Nature Reviews Cancer (2012)

CTCs PRESENT
Technology

< 40 devices for
CTCs isolation
commercialized

Miyamoto el al. Nature Reviews Clinical Oncology 11, 401–412 (2014)

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 PRESENT
CTCs in vitro/ ex vivo expansion

CTCs PRESENT
CTCs ex vivo expansion
Ex vivo culture of circulating breast tumor cells for individualized testing of drug
susceptibility

Yu et al. Science 2014

CTCs PRESENT
Ex vivo culture of circulating breast tumor cells for individualized testing of drug
susceptibility

Yu et al. Science 2014

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

CTCs PRESENT/CLINICAL VALIDATION

Cabel et al., Int J Clin Oncol, 2017

ctDNA PRESENT
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

Wan et al. Nat Rev
Cancer 17 (4), 223238. 2017

ctDNA PRESENT
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%

COBAS (ROCHE)

• 42 mutaciones en EGFR
• Sensibilidad por mutaciones activadoras: 82%
• Especificidad: 98%

ctDNA PRESENT

Idylla (Biocartis)

ctDNA PRESENT

ctDNA PRESENT

FUTURE

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

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
 Could we use Liquid biopsy for cancer screening?
 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?

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

FUTURE
CLINICAL TRIALS INCLUDING CTCs

TOTAL 2876
Completed 1235
Active 1328

https://clinicaltrials.gov/

FUTURE
CLINICAL TRIALS INCLUDING ctDNA

TOTAL 277
Completed 45
Active 205

https://clinicaltrials.gov/

FUTURE
CLINICAL TRIALS INCLUDING ctDNA IN USA

https://clinicaltrials.gov/

FUTURE
Liquid biopsy heating up, but is it
a big data problem?
Liquid biopsy analysis will provide a
large amount of data that we need
to intepret together with clinical
parameters to reach
PRECISION ONCOLOGY

CONCLUSION
PRESENT/FUTURE OF LIQUID BIOPSY
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

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."
Dr. Baselga
“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”

ES LA LECHE ESTO
DE LA BIOPSIA
LÍQUIDA¡¡

YA VEREMOS

GRACIÑAS¡¡

FUTURE
Technological development and validation

Siravenga et al., Nature Rev 2017

CTCs PRESENT

Novello et al Metastatic
Non-Small-Cell Lung
Cancer: ESMO Clinical
Practice Guidelines
Annal Oncol 2016