By Rachel Pugh
Ignoring the part played by tumour evolution may comprise the effectiveness of new cancer treatments.
Dr Mariam Jamal-Hanjani, Senior Clinical Lecturer and Consultant Medical Oncologist at UCL Cancer Institute in London, expressed her hope that future clinical trials would be adapted to take into account tumour evolution to move towards bespoke treatments for patients with cancer.
The heterogeneity of cancer cells provides insight into the causes and progression of a disease.
Dr Jamal-Hanjani explained that tumour cells evolve along Darwinian lines leading to mutations at a cell and a chromosomal level. Multiregion sequencing can map the course of non-small-cell lung cancer (NSCLC) evolution, revealing the presence of clonal (or truncal) mutations in every cancer cell. Sub-clonal branches are evident in subpopulations of cancer cells. Extensive intra-tumour heterogeneity leads to genomic instability at the mutational and chromosomal level.
One reason heterogeneity is clinically important is that it allows for a prediction about the course of the disease. The proportion of sub-clonal somatic copy number aberrations (SCNAs) in a tumour is a predictor of death or disease recurrence. A disappointing number of studies take into account heterogeneity and tumour evolution.
Making use of heterogeneity therapeutically requires targeting multiple trunk/clonal events in every cell, with each patient needing a unique therapy, without immune destruction. This is currently very expensive.
Current research is looking at tumour neoantigens. Dr Jamal-Hanjani is involved in a Phase 1/2 study with Achilles Therapeutics using clonal neoantigen targeting T cells (cNeT) in patients with metastatic or recurrent lung cancer. The study is expected to enrol the first patient later in 20191.
Greater knowledge of tumour evolution will change the way clinical trials are carried out. It will also permit interventions to take place in a patient with residual disease, at a point when intra-tumour heterogeneity is low.
Many questions still remain about how cancer evolution can be predicted and constraints harnessed, but Dr Jamal-Hanjani said: “It could be that with more study of more cancers we will be able to come up with evolutionary rule books. This might enable us to offer patients combination therapies and to stay one step ahead of the tumour.”