Over 90% of new cases of cancer are solid cancer types, the most common of which in Europe and North America are breast, lung, colorectal and prostate. Many solid tumours still have dismal prognoses: pancreatic and brain cancers in particular, whilst others can only be successfully treated by drastic surgeries that result in life-changing consequences, such as limb amputation to remove a metastatic bone tumour.
Cancers are predicated on cells with genetic mutations. However, we harbour many cells with genetic mutations at any point in time, increasingly so as we age, yet the vast majority of these do not lead to tumours. Whilst genetic mutations are a necessary condition for cancer, they are not a sufficient condition. The mutated cell must be in a tumour-permissive environment for a tumour to establish, just as a plant seed must have fertile soil and the right conditions to germinate and grow.
The extracellular matrix is perhaps the most important part of creating - or not - the right conditions for a tumour to establish from a mutated cell. The structure and composition of the extracellular matrix in and around a tumour is usually very different to that in the host tissue, indeed changes to the extracellular matrix are some of the earliest events in tumourogenesis, perhaps because of the requirement for a tumour-permissive environment to estalish a tumour. Like all cells, cancer cells take instructions in their behaviour from the surrounding extracellular matrix. As the matrix structure changes more and more with the cancer progression, so that altered matrix structure provides signals to cancer cells to become more invasive, and to other cells nearby to support the tumour growth.
For a tumour to grow, cancer cells must (directly or indirectly) remove some of the surrounding extacellular matrix or stretch it to make space for the growing tumour. For metastatic cancer cells to invade further into the tissue and to migrate to other tissues, they must force tunnels through the surrounding extracellular matrix through which they can move. This necessitates either degradation or deformation of extracellular matrix along the route the cancer cells take.
The specificity of the extracellular matrix composition and structure to the tumour compared with the host tissue matrix, the requirement of cancer cells to navigate the surrounding extracellular matrix and the fact that the extracellular matrix molecular structures contain an important instruction set to cancer cells (and other cells in the local region) suggested to us that we may be able to treat tumours by chemically manipulating the tumour extracellular matrix - either to prevent cancer cells from being able to move through it or by changing the instruction set the matrix presents to the cancer cells. This is a completely new paradigm in medicine; drugs normally work by disrupting chemical processes inside cells. We reasoned that in a tumour, where there are many different types of cancer cells with different sets of genetic mutations and different metabolism, that an approach of treating the tumour environment could be more effective than trying to treat cancer cells directly, as we are effectively treating all cells in the tumour regardless of their type.
The Duer research group is actively pursuing this new matrix therapeutics cancer treatment paradigm in glioblastoma and pancreatic ductal adenocarcinoma, with two patent applications already submitted (PCT/GB2021/050345 (WO2021/161034); PCT/GB2022/052082).
Professor Duer founded Cambridge Oncology Ltd in 2018 in order to develop pipelines for new drugs resulting from this research to reach patients.