Cancer Metastasis

Group Leader: Professor Mariam Jamal-Hanjani

---

Research

Metastatic disease is the main cause of death in patients diagnosed with cancer and in our lab, we are interested in studying the evolutionary and biological processes associated with cancer metastasis by analysing tumours from early to late stage disease.  In particular, we work with research autopsy samples from the PEACE study, which provides a unique opportunity to study the landscape of metastatic disease in the context of the tumour microenvironment.  

Using a multi-omics approach, we aim to trace the dynamics of the cancer genome, transcriptome, metabolome and host immune system to identify the underlying mechanisms driving the metastatic process and the impact these have on clinical outcome and ultimately death.  Whilst it is known that cancer cells tend to use pathways of energy metabolism that are distinct from normal healthy cells, little is known about how cancer metabolism can impact tumour evolution and the host immune response. To explore this, we are investigating the metabolic mediators that play a role in metastases and that associate with a catabolic state and altered body composition suggestive of cancer-associated cachexia.  

By identifying the features and behaviour of aggressive cancers destined to metastasise and the drivers of metastatic disease despite treatment, we have the potential to identify mechanisms of drug resistance and novel therapeutic opportunities that may benefit future patients. Furthermore, gaining insights into the tumour- and host-specific factors driving altered body composition in early to late stage disease may help identify predictive and/or prognostic biomarkers to guide early interventional strategies and novel therapeutic opportunities to prevent or delay the development of cancer-associated cachexia and subsequent disease progression.  

---

The PEACE Study

PEACE is a national research autopsy programme that has been recruiting patients and performing autopsies since 2016 with the intention of understanding the mechanisms involved in cancer progression and drug resistance. It aims to study cancer evolution in the context of the tumour microenvironment and immune landscape, and to identify the biological processes leading to metastatic disease and subsequent death.

PEACE study links

• Finding PEACE and remembering my brother Mark – Dave’s story, CRUK blog
• Post-mortem cancer study goes national, CRUK press release 
• Skin cancer - Mark's story (YouTube) CRUK
• Bodies are revealing the secrets of how cancer kills, Wired
• Scientists say ‘thank you’ to cancer trial participants, Telegraph

---

Selected publications

• Karasaki, T. et al…Jamal-Hanjani, M. (2023). Evolutionary characterisation of lung adenocarcinoma morphology in TRACERx. Nature Medicine, 2023

• Al-Sawaf, O. et al…Jamal-Hanjani, M., Swanton, C. (2023). Body composition and lung cancer-associated cachexia in TRACERx. Nature Medicine, 2023

• Al-Bakir, M. et al…Jamal-Hanjani, M., McGranahan, N., Swanton, C. (2023). TRACERx: The evolution of metastases in non-small cell lung cancer. Nature, 2023

• Frankell, A M. et al… Jamal-Hanjani, M., McGranahan, N., Swanton, C. (2023). The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature, 2023

• Hill, W. et al…Jamal-Hanjani, M., Swanton, C. (2023). Lung Adenocarcinoma Promotion by Air Pollutants. Nature, 2023

• Abbosh, C. et al…Jamal-Hanjani, M., Birkbak, N., McGranahan, N., Swanton, C. (2023). High resolution phylogenetic ctDNA tracking predicts relapse risk and metastatic dissemination patterns in early-stage lung cancer. Nature, 2023

• Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S et al. Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017 
   
• Abbosh C*, Birkbak NJ*, Wilson GA*, Jamal-Hanjani M* et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 *Joint first author  
   
• Turajlic S, Xu H, Litchfield K, Rowan A, Chambers T, Lopez JI, Nicol D, O'Brien T, Larkin J, Horswell S, Stares M, Au L, Jamal-Hanjani M et al. Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell. 2018 
   
• Rosenthal R, Cadieux EL, Salgado R, Bakir MA, Moore DA, Hiley CT, Lund T, Tanić M, Reading JL, Joshi K, Henry JY, Ghorani E, Wilson GA, Birkbak NJ, Jamal-Hanjani M et al. Neoantigen-directed immune escape in lung cancer evolution. Nature. 2019 

Publications

• Chemi F, Rothwell DG, McGranahan N, Gulati S, Abbosh C, Pearce SP, Zhou C, Wilson GA, Jamal-Hanjani M et al. Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse. Nat Med. 2019 
   
• 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,  et al. A clonal expression biomarker associates with lung cancer mortality. Nat Med. 2019 
   
• Joshi K, Robert de Massy M, Ismail M, Reading JL, Uddin I, Woolston A, Hatipoglu E, Oakes T, Rosenthal R, Peacock T, Ronel T, Noursadeghi M, Turati V, Furness AJS, Georgiou A, Wong YNS, Ben Aissa A, Werner Sunderland M, Jamal-Hanjani M et al. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat Med. 2019 
   
• López S, Lim EL, Horswell S, Haase K, Huebner A, Dietzen M, Mourikis TP, Watkins TBK, Rowan A, Dewhurst SM, Birkbak NJ, Wilson GA, Van Loo P, Jamal-Hanjani M et al. Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution. Nat Genet. 2020 
   
• Litchfield K, Stanislaw S, Spain L, Gallegos LL, Rowan A, Schnidrig D, Rosenbaum H, Harle A, Au L, Hill SM, Tippu Z, Thomas J, Thompson L, Xu H, Horswell S, Barhoumi A, Jones C, Leith KF, Burgess DL, Watkins TBK, Lim E, Birkbak NJ, Lamy P, Nordentoft I, Dyrskjøt L, Pickering L, Hazell S, Jamal-Hanjani M et al. Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue. Cell Rep. 2020 
   
• AbdulJabbar K, Raza SEA, Rosenthal R, Jamal-Hanjani M et al. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma. Nat Med. 2020 
   
• Ghorani E, Reading JL, Henry JY, de Massy MR, Rosenthal R, Turati V, Joshi K, Furness AJS, Aissa AB, Saini SK, Ramskov S, Georgiou A, Sunderland MW, Wong YNS, De Mucha MV, Day W, Galvez-Cancino F, Becker PD, Uddin I, Ismail M, Ronel T, Woolston A, Jamal-Hanjani M et al. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nat Cancer. 2020