NEW YORK – The new International Alliance for Cancer Early Detection plans to assess a great variety of tests and approaches as it works to develop new strategies and technologies for early-stage diagnosis of cancer in coming years.
Cancer Research UK and partners at the University of Cambridge, the University of Manchester, and University College London in the UK, and Stanford University and Oregon Health and Science University in the US, announced the effort earlier this month. CRUK has pledged £40 million ($52 million) over the next five years to support ACED, while the US partners will invest $20 million.
The number of technologies to be assessed is vast, and ranges from liquid biopsies and molecular imaging to immunohistochemistry and RNA-seq. Each of the centers involved has extensive experience in early-stage cancer testing and a trove of resources to draw upon for the project.Â
According to CRUK, the partners plan to engage pharmaceutical and biotechnology companies to make new tests and therapies available to patients as quickly as possible.
Discussions are underway to determine what are the most promising approaches to trial among the five centers in coming years. Sadik Esener, director of the Cancer Early Detection Advanced Research Center (CEDAR) at the OHSU Knight Cancer Institute, said that ACED's priorities will be on developing better screening tools, followed by new diagnostics, and then on imaging and therapeutics.
"It's a hierarchical way of treating early cancers," Esener said. "For that we need a slew of new technologies," he said. "Then we can decide at what level each technology has to come in."
OSHU has an abundance of techniques and tests at its disposal as it enters the alliance. Recently published work has included using next-generation sequencing to detect minimal residual disease in acute myeloid leukemia patients as well as the development of a platform-agnostic approach for detecting circulating tumor cells in prostate cancer patients.
Esener said that OSHU has been investing in liquid biopsies and is developing a biochip capable of detecting Stage II cancer patients, particularly in pancreatic cancer. There has also been a focus on single-cell sequencing and RNA-seq. "This is similar to what people use for noninvasive prenatal testing," he said, "but applying it to cancer testing."
Esener also said OSHU has worked on cancer nanobiology tools and "state-of-the art" microscopy capabilities that support immunohistochemistry work. "This gives us a good idea on how cells are distributed in tumors, what kinds of proteins each cell is creating," he said.
For OSHU, the benefit of the alliance is working with other centers. "We have been at the forefront of precision oncology," said Esener. "But we want to do things by collaboration."
He noted the center has worked with partners at the Canary Center at Stanford for Early Cancer Detection in the past. Like CEDAR, the Canary has extensive resources to put to use in the new alliance, with core facilities devoted to clinical imaging, proteomics, and cell and molecular biology. Various labs within the Canary focus on employing microfluidics and other technologies in molecular diagnostics. Representatives for the center did not reply to queries seeking comment. In a statement, the center referenced projects related to nanosensors, optical and optoacoustic imaging technologies, immune-diagnostics, and other approaches.
British clinical translation
Like their partners at OSHU and Stanford, the UK ACED centers have similar technology resources at their disposal. However, applying new tests developed by the alliance in a clinical setting is also part of their goals. The University of Cambridge, for instance, will develop and implement the Clinical Infrastructure for Research in Early Detection, a clinical facility that will support early-phase clinical trials of new diagnostics for the new alliance.
Rebecca Fitzgerald, co-lead of the Cancer Research UK Cambridge Center's early cancer detection program, said that Cambridge is "focusing on the clinical translation," as well as joining the efforts to understand cancer biology and to identify new technologies.
"Molecular tests and in vitro diagnostics are certainly part of our remit and we have a number of such technologies in various stages of development," she added.
"In Cambridge, we will focus on clinical translation," said Wendy Alderton, early detection program manager at the Cancer Research UK Cambridge Center. "We will do first-in-man studies of new technologies as they come through," she said.
Early cancer detection techniques already under development at Cambridge include imaging tools to detect pre-cancerous lesions, methods for detecting circulating tumor cells, as well as methods for measuring methylation in CTCs.
"There are a lot of people working on circulating tumor DNA, but much of the work has been on recurrence," Alderton said. "There is a big push in the field to make it sensitive enough to detect fragments of DNA coming from early tumor, to push [the technology] to be able to detect tumors at stage I or II," she added. "We are looking to detect tumors before they spread so you can really make a difference in outcomes."
One project underway at Cambridge involves using blood-based markers to detect prostate cancers with poor prognoses and is being carried out with investigators at the Canary Center at Stanford. "In Cambridge, there is a lot of early-stage work in different blood-based markers," noted Alderton. She noted that Cambridge has been working to prioritize these approaches to get them into clinical studies, where the center will not only evaluate performance, but also health economics. "These technologies have to be cost effective," she said.
Like Cambridge, Manchester will also serve as a proving ground for new tests coming out of the new alliance.
"We want to turn Manchester into a place where we can test out new ideas," said Martin Bone, who is the ACED programme manager at the Cancer Research UK Manchester Institute. "We want to establish ourselves so that when we develop new ideas, technologies, and diagnostic tools through this alliance, Manchester has early access to them," Bone said. He noted that due to the unique healthcare system in Manchester and the large diverse population of over 3.2 million people, Manchester is the ideal place to develop and deploy new early detection research.
The Manchester healthcare system already has experience with public engagement and outreach. One example of this in practice is the Lung Health Check, which involves going out to the public, identifying those at higher risk through questionnaires, and analyzing them through further screening methods. "This is especially beneficial for those harder-to-reach populations," Bone noted.
According to Bone, Manchester would like to extend this approach to breast cancer screening. "We want to do low-dose mammography, questionnaires, scanning, everything in a single package," Bone said.
The Manchester team will also aim to create living tissue banks of pre-cancerous tissues to explore ways to combat cancer gene activation and use artificial intelligence to analyze results quicker.
According to Bone, Manchester already has a historical relationship with Cambridge, and ongoing collaborative projects will be a cornerstone of the alliance. While the number of programs and projects accessible to the alliance appears limitless, he said the executive board of the alliance will ultimately decide on what projects will be funded. "All key decisions sit with them," he said.
University College London is the third UK center involved in the alliance and will also provide significant resources for clinical translation. According to CRUK, its ACED center will host 24 investigators across UCL and its partner, NHS trusts. It will have access to 200,000 patients for clinical trials as part of the alliance.
"These are magnificent cohorts that we will be able to tap into," OSHU's Esener acknowledged. "It's an amazing opportunity for the institutions and cancer patients that these institutions are putting their resources together."