If curing cancer is a jigsaw puzzle, then scientists have most of the pieces but are still struggling to put it all together. To date, researchers have sequenced over a million different tumours hunting for genes that trigger or accelerate cancer. Despite significant breakthroughs, experts suggest that most of these studies only provide a limited and coarse view of cancer’s complexities.
Cancer is a genetic disease driven not just by alterations to the DNA, but by additional epigenomic and transcriptomic pathways, explained Patrick Tan, Executive Director of A*STAR’s Genome Institute of Singapore (GIS). “In the past, profiling cancers at these multiple or multimodal levels was prohibitive due to technical limitations and high cost,” Tan added.
Now, a review of the cancer genome landscape by Tan and colleagues provides a fresh take on solving the cancer puzzle. Leveraging next-generation profiling technologies will be key to unlocking more holistic, comprehensive views of the entire tumour ecosystem. These multimodal datasets could ultimately reshape treatment strategies to dramatically improve patient outcomes.
One prime example is how primary and metastatic tumours may be genetically identical, but their genes’ chemical signatures (known as the epigenome) can be totally different. “These changes in the epigenome can ultimately produce gene expression programmes that cause aggressive cancer behaviour and drug resistance,” said Tan, adding that collecting epigenomic data could reveal new drug targets that would previously have been missed or lead to more accurate diagnostic tests.
It’s also important to consider how other cells in the tumour ecosystem—immune cells, fibroblasts, and cells lining blood vessels—are changing as tumours progress. “Immune cells in tumours show expression patterns of exhaustion, where they can’t mount an effective immune attack,” said Tan. “These non-genetic changes must also be considered to identify which patients are likely to benefit from cancer immunotherapy.”
Tan predicts that emerging single-cell technologies will soon allow researchers to track genetic, epigenomic, and transcriptional changes across 3-dimensional space and time. Connecting the dots between these datasets could pave the way for what Tan describes as a “tumour Google map” for scientists to successfully navigate the complex cancer landscape.
It is proposed that new frameworks should be established for collecting cancer data. “Cancer centres should establish umbrella protocols where patients are consented to multi-modal cancer profiling across their treatment regimen to understand individual patient trajectories across the cancer life cycle,” Tan concludes.
The A*STAR-affiliated researcher contributing to this work is from the Genome Institute of Singapore (GIS).