October: dr. Allan Interview

Journey of Circulating Tumour Cell Detection from Bench to Bedside Interview with Dr. Alison Allan

Sareh Bagherichimeh, HBSc.
Contact: sbagher4@uwo.ca
October 2021
Interview Sept 30th, 2021

Have you ever wondered how a hunch or a hopeful idea is followed up on and developed into a treatment or detection method in cancer? 

For breast cancer month, we sat down with Dr. Alison Allan to learn about translational research; how scientific discoveries in the laboratories develop from studying how cancer cells work into approaches to medical care that improve the lives of breast cancer patients. 

As the Director of the Research Cancer Society of Canada Translational Research Unit at the London Health Sciences Centre, Dr. Allan takes scientific discoveries made in the laboratory and works to develop them into approaches to medical care. Cancer is caused by cells that start growing uncontrollably. Though it originates in the region native to the cancer cells, it can spread to other regions of the body via the blood or the lymphatic system. Her research focuses on cancer metastasis, the spread of cancer cells in the body. Our current standard of care methods are better equipped to identify and remove tumours before they metastasize. However, once cancers metastasize, treatment becomes a lot more difficult. As a result, the majority of cancer related deaths occur due to the effects of metastasis. [1] 

Metastasis is a multi-step event that begins when cancer cells leave the initial tumour site and spread to the bloodstream where they have to survive in circulation. Eventually, the cancer cells may come to a stop at another area in the body to then invade and grow. This is the secondary site where they continue their uncontrolled growth. [2] Given the multi-step nature of the metastasis, there are several opportunities for early identification and therapeutic targeting of metastatic cells before it becomes detrimental to the health of patients. (Figure 1)

 

Cancer cells travelling through the bloodstream are called circulating tumour cells (CTCs). There is growing evidence that the presence of CTCs in the blood may be an important predictor of potential metastasis, as well as an indicator of poor outcomes. [3,4] Despite the discovery of CTCs over a century ago, the lack of a sensitive and reliable technology for detection and quantification of these CTCs has limited our ability to study and effectively identify CTCs in routine clinical practice. [5] 

The ability to consistently identify and quantify CTCs in cancer patients is showing a lot of promise, not only in early diagnosis of metastatic disease, but also as a way to potentially  monitor disease recurrence and response to treatment. Molecular characterization of CTCs could potentially be the basis of the development of targeted therapies. [5] Dr. Allan believes ongoing co-operation between scientists in various fields, from basic biology researchers and clinical scientists, to doctors and companies, is crucial for the realisation of CTCs’ true potential in improving the lives of cancer patients. 

Dr. Allan started out in basic science; it was while studying cancer metastasis in mice models that she initially came across the need to develop techniques for identifying and quantifying the circulating tumour cells. Ever since, she has been working on translating these findings to develop techniques for detecting and quantifying CTCs in cancer patients for diagnosis and treatment monitoring. She is currently in collaboration with clinicians and technology leaders running multicentre cancer clinical trials. Dr. Allan believes there needs to be a balance between  furthering our basic understanding through basic scientific research and translational research that focuses on applying the knowledge to patient and healthcare needs. As such, Dr. Allan’s lab works to better understand this poorly understudied area of cancer research as a whole. Dr. Allan’s lab simultaneously works to further our basic scientific knowledge while also working on applying the scientific findings, so that current therapies can be better utilized to target the metastatic disease and used to develop more effective therapies that prevent or reverse cancer metastasis.

As one of the lead Canadian scientists studying and developing new technologies for the detection and analysis of CTCs in the blood, Dr. Allan has co-chaired workshops bringing together clinicians and researchers from academic and private sectors to address the challenges of implementing technologies for detecting CTCs in the clinic. [6] One of Dr. Allan’s main objectives of putting together such initiatives is to fuel collaborations between researchers and clinicians. She is passionate about the importance of circular dialogue

between scientists and clinicians of different disciplines. By maintaining collaborations with clinicians, Dr. Allan says she has gained a better understanding of the current challenges in cancer treatment and detection as well as appreciation for the heterogeneity of cancer. She has also seen the clinicians gain an appreciation of the complexity of the underlying processes of cancer biology. Dr. Allan believes “understanding and respecting what each party brings to the table” is key for fruitful interdisciplinary partnership. (Figure 2)

Difference between basic and translational research:

*Modified from the NCI translational research working group (2006)

Clinical Studies 

Research with human subjects that is:

1. Patient-oriented research. Research conducted with human subjects (or on the material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. It includes: (a) mechanisms of human disease, (b), therapeutic interventions, (c) clinical trials, or (d) the development of new technologies.
2. Epidemiological and behavioral studies.
3. Outcomes research and health services research.

*Source: grants.nih.gov

Resources/Recommendation for patients:  

Dr. Allan stresses the importance of educating patients to empower them to participate in their cancer treatment. Working closely with clinicians and patients, she has developed a passion for educating patients about their diagnoses, as well as the scientific process. More specifically, she wants others to know how vital clinical trials are in the development of better treatments, detection, and prognosis, and what an indispensable role patients can play by participating in clinical trials.

Online resource 

• Quality Cancer Treatment
• Cancer care Ontario 

Books 

• Book: Taking charge of Cancer 

Written by Dr. David Palma, a friend of Dr. Allan, to empower cancer patients. It provides a uniquely Canadian perspective to educate and guide cancer patients through the Canadian health care system. 

References

1. Canadian Cancer Statistics 2008, National Cancer Institute of Canada: Toronto, Canada, 2008 http://www.cancer.ca.
2. A.F.Chambers, A. C. Groom, andI.C.MacDonald, “Dissemination and growth of cancer cells in metastatic sites,” Nature Reviews Cancer, vol. 2, no. 8, pp. 563–572, 2002.
3. K. Pantel,R.H.Brakenhoff, and B. Brandt, “Detection, clinical relevance and specific biological properties of disseminating tumour cells,” Nature Reviews Cancer, vol. 8, no. 5, pp. 329– 340, 2008.
4. T. R. Ashworth, “A case of cancer in which cells similar to those in the tumours were seen in the blood after death,” TheMedical Journal ofAustralia, vol. 14, pp. 146–149, 1869.
5. Lowes LE, Bratman SV, Dittamore R, Done S, Kelley SO, Mai S, Morin RD, Wyatt AW, Allan AL. Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation. Int J Mol Sci. 2016 Sep 8;17(9):1505.

*Figure 1 created with BioRender.com