Translational Research at the Institute of Cancer Research

Principal investigators: Professor Richard Houlston and Dr Martin Kaiser

Institution: Institute of Cancer Research, London

Award amount: £1,985,656

Duration: 5 Years

Project status: Active

Although treatments have improved over the last decade, myeloma remains incurable. Current treatments can cause side effects and myeloma cells eventually become resistant so a treatment becomes less effective. We need to understand what causes myeloma to develop in the first place and how it develops resistance to treatment so we can prevent that happening.

The research programme uses state-of-the-art laboratory techniques and high-performance computer analytics to assess the entire genetic make-up of myeloma cells. This helps us to understand which genetic changes are important and what effect they have within the myeloma cells.

The research programme has three inter-related projects:

Host factors in multiple myeloma is looking at who develops myeloma and why. This will help us to understand the very early stages of myeloma development and the risk factors involved. This could help to prevent or delay the onset of myeloma.

Mechanisms of transformation and drug resistance in myeloma investigates the genetic changes that occur as treatments stop working, and to identify which genes are helping the myeloma cells survive. This will help to find new drug targets or ways to make existing treatments more effective.

Drug discovery and development is analysing the mechanism of a new drug which is currently in clinical trials. The team are screening myeloma cells in the laboratory to understand why the drug is less effective in some late stage patients and which genes are involved. This could help to identify ways to make this drug more effective in these patients.

How this research project will help myeloma patients

Understanding the changes that occur in myeloma cells, particularly when they become resistant, will help us to understand the pathways that are helping cells to avoid the effects of the chemotherapy. This could help to identify new or re-purposed drugs that block these effects making the myeloma cells more vulnerable to chemotherapy. Understanding the changes that occur as myeloma progresses would help to personalise a patient’s treatment such that they receive the chemotherapy that may be most beneficial to them.

Key Outputs

Croft et al., (2021) Copy number evolution and its relationship with patient outcome-an analysis of 178 matched presentation-relapse tumour pairs from the Myeloma XI trial. Leukaemia.
Read more: https://pubmed.ncbi.nlm.nih.gov/33262523/

Went et al., (2020) Search for multiple myeloma risk factors using Mendelian randomization. Blood Advances.
Read more: https://pubmed.ncbi.nlm.nih.gov/32433745/

Hoang et al., (2020) An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics. Blood Cancer Journal
Read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560599/

Pertesi et al., (2020) Genetic predisposition for multiple myeloma. Leukemia.
Read more: https://pubmed.ncbi.nlm.nih.gov/31913320/

Hoang et al., (2019) Mutational processes contributing to the development of multiple myeloma. Blood Cancer Journal.
Read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684612/

Went et al., (2019) Transcriptome-wide association studies of multiple myeloma identifies candidate susceptibility genes. Human Genomics.
Read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700979/

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