cancer evolution

birkbak group

We apply computational approaches to study cancer evolution from a translational perspective.

Our mission is to understand cancer evolution at the molecular level, and to build tools and develop methods that use this information to improve patient treatment.

Nicolai Birkbak has a background in cancer biology, biomarker development, translational cancer research and cancer evolution and heterogeneity based on research undertaken at Technical University of Denmark (PhD and postdoc), Dana-Farber Cancer Institute (postdoc), and University College London & the Francis Crick Institute (senior postdoc).

Nicolai Juul Birkbak at Google Scholar

Cancer evolution

Key steps in carcinogenesis, © Nicolai Birkbak

An essential question in cancer research today and a focus of our research is understanding the key steps in carcinogenesis: how cells develop from a normal state to malignant cancer through benign, invasive and metastatic disease.

Over recent years, exponential drop in Next Generation Sequencing costs coupled with significant investment in cancer research has led to the creation of large cancer cohorts with extensively characterized tumor samples. This effort has improved our understanding of cancer as a molecular disease, but a focus on driver events has so far not led to a breakthrough in patient therapy, and patient survival has not significantly benefited.

While the dominant focus in the community remains tumor-centric, it has become increasingly clear that non-cancer cells play an active role in carcinogenesis and in the development of metastatic disease.

As part of our exploration of the drivers of cancer metastasis, we have started to investigate how patient health, demographics, and immune competency may play an active role in both suppressing and promoting cancer development and cancer metastasis.

Host factors for carcinogenesis, © Nicolai Birkbak

Metastatic dissemination and effect of treatment

Our lab utilizes cancer NGS data and computational tools to mine the developmental history on individual cancers, and to determine clonality of events.

In this manner, we aim to describe the order of carcinogenic events and to infer potential drivers of metastatic dissemination. This allows us to construct evolutionary trajectories for individual cancer types, potentially informing about likely changes malignant cells may be biased towards when subjected to anti-cancer therapy.

This opens the door to therapeutic approaches where treatment may be directed towards likely cancer clones not yet observed in a given sample.

Metastatic dissmination, © Christensen et al, Cancer Research, 2022.

Tracking cancer in vivo

To utilize our improved understanding of cancer therapeutically, properly characterizing and tracking cancer evolution in real time is vital.

While a tissue biopsy remains the most informative, it cannot be performed at high frequency due to costs and discomfort. Non-invasive technologies such as liquid biopsies and radiomics analysis of medical imaging data are comparatively cheap and can be performed at high frequency.

We utilize both tumor-informed approaches such as cancer-type specific ctDNA assays, and tumor agnostic approaches such as whole-genome ctDNA and T-cell receptor sequencing to characterize cancer biology, residual disease, patient-specific immune-capacity and treatment response in real-time, providing the treating clinician with crucial information about how to intervene, and when.

Liquid biopsies are very useful for tracking cancer in vivo and make treatment decisions, ©Nicolai Birkbak

Software

Defining cGAS-STING activity in cancer

https://github.com/mxs3203/csg_prediction

Original publication: Classifying cGAS-STING activity links chromosomal instability with immunotherapy response in metastatic bladder cancer

GENIUS: Multiomics data analysis based on spatial transformation

https://github.com/mxs3203/genome_mapped_to_image

Original publication:GENIUS: GEnome traNsformatIon and spatial representation of mUltiomicS data

Group leader

Nicolai Birkbak

Assoc. Professor, PhD, MSc, Group leader

People

Asbjørn Kjær

PhD student, MSc

Johanne Ahrenfeldt

Postdoc, MSc, PhD

Judit Kisistók

Postdoc, MSc, PhD

Laura Andersen

PhD student, MSc

Mateo Sokač

Postdoc, PhD, MSc

Randi Istrup Pedersen

Postdoc, PhD, MSc

Collaborations

TRACERx

We are very excited to be part of the UK-based TRACERx (Tracking Cancer Evolution Through Therapy) consortium, tracerx.co.uk, led by Professor Charles Swanton at the Francis Crick Institute, London, UK.
Here we particularly contribute to the analysis of ctDNA-based phylogenetic tracking of cancer evolution during therapy.

Selected Publications

Artificial intelligence in cancer imaging: Clinical challenges and applications. Bi WL, Hosny A, Schabath MB, Giger ML, Birkbak NJ, Mehrtash A, Allison T, Arnaout O, Abbosh C, Dunn IF, Mak RH, Tamimi RM, Tempany CM, Swanton C, Hoffmann U, Schwartz LH, Gillies RJ, Huang RY, Aerts HJWL.CA
Cancer J Clin. 2019 Mar;69(2):127-157. doi: 10.3322/caac.21552. Epub 2019 Feb 5. Review. PubMed

Tracking the Evolution of Non-Small-Cell Lung Cancer Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, Shafi S, Johnson DH, Mitter R, Rosenthal R, Salm M, Horswell S, Escudero M, Matthews N, Rowan A, Chambers T, Moore DA, Turajlic S, Xu H, Lee SM, Forster MD, Ahmad T, Hiley CT, Abbosh C, Falzon M, Borg E, Marafioti T, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Shah R, Joseph L, Quinn AM, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Dentro S, Taniere P, O'Sullivan B, Lowe HL, Hartley JA, Iles N, Bell H, Ngai Y, Shaw JA, Herrero J, Szallasi Z, Schwarz RF, Stewart A, Quezada SA, Le Quesne J, Van Loo P, Dive C, Hackshaw A, Swanton C; TRACERx Consortium.
N Engl J Med. 2017 Jun 1;376(22):2109-2121. doi: 10.1056/NEJMoa1616288. Epub 2017 Apr 26. PMID: 28445112 PubMed

Treatment represents a key driver of metastatic cancer evolution. Christensen DS, Ahrenfeldt J, Sokač M, Kisistók J, Thomsen MK, Maretty L, McGranahan N, Birkbak NJ.
Cancer Res. 2022 Jun 22:canres.CAN-22-0562-E.2022. doi: 10.1158/0008-5472.CAN-22-0562. Online ahead of print. PubMed

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Grönroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium, Swanton C.  Nature. 2017 Apr 26;545(7655):446-451. doi: 10.1038/nature22364. Erratum in: Nature. 2017 Dec 20;: PMID: 28445469; PMCID: PMC5812436. PubMed

A clonal expression biomarker associates with lung cancer mortality. Biswas D, Birkbak NJ, Rosenthal R, Hiley CT, Lim EL, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore DA, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins TBK, Veeriah S, Wilson GA, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan AM, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C; TRACERx Consortium.
Nat Med. 2019 Oct 7. doi: 10.1038/s41591-019-0595-z. [Epub ahead of print] PubMed

Cancer Genome Evolutionary Trajectories in Metastasis. Birkbak NJ, McGranahan N.
Cancer Cell. 2020 Jan 13;37(1):8-19. doi: 10.1016/j.ccell.2019.12.004. Review. PubMed

Graduations

Name
Title
Year
Grade
Ditte Siggaard Christensen
Deciphering the evolution of metastatic cancer
2023
PhD
Janne Engestoft
Identifying Copy Number Signatures by Latent Dirichlet Allocation
2022
MSc
Laura Andersen
Characterizing the role of tumor growth dynamics and proliferation in ctDNA release
2022
MSc
Asbjørn Kjær
Establishing a pipeline for analysis of T-cell receptor sequencing data and characterizing the impact of the T-cell repertoire on the clinical outcome of bladder cancer
2022
MSc
Mateo Sokač
Artificial Intelligence in Medicine: Using machine learning to improve patient stratification for precision medicine
2022
PhD
Mateo Sokač
Utilization of Artificial Intelligence Towards Precision Medicine: Interplay Between Chromosomal Instability and Immune System
2020
part A / MSc

Bioinformatics

skou Pedersen Group
computational genomics & transcriptomics
Link her
Besenbacher Group
computational genomics
Link her