Cancer Dormancy and Tumor Microenvironment Institute to Take Research Efforts to Greater Heights

Julio Aguirre-Ghiso, PhD

The Cancer Dormancy and Tumor Microenvironment Institute, which has recently been launched at Albert Einstein Cancer Center, will focus on taking the tumor microenvironment research being done at the center to the next level and to develop novel technologies that can better identify dormant cancer as well as prevent and control recurrent disease.

“One of the goals of the institute is to open our eyes to other opportunities that that may be available that are not commonly used to treat metastatic disease to detect it [and] to understand how it's progressing,” Julio Aguirre-Ghiso, PhD, founding director of the institute. “We need to understand that better because we could spare [patients] from unnecessary and usually [difficult]-to-tolerate treatments. We want to change the culture a little bit in how we treat the disease by bringing [the] biology to the forefront.”

In an interview with OncLive^®, Aguirre-Ghiso, who is also the director of the Gruss-Lipper Biophotonics Center and co-leader of the AECC Tumor Microenvironment and Metastasis Program at Albert Einstein Cancer Center, discusses goals for the institute and the unmet needs in the field of oncology that it will seek to address.

OncLive^®: Could you speak to the need for the Cancer Dormancy and Tumor Microenvironment Institute?

Aguirre-Ghiso: The efforts in cancer research and treatment have been phenomenal [and we have made] progress toward detecting cancer earlier and finding new ways to harness the immune system. These advances have improved patient outcomes. However, there is still a large challenge [with] metastatic disease. Metastatic disease usually presents as symptomatic, and sometimes in multiple organs, [proving] difficult to treat. [Some patients] respond very well [to treatment], but overall, we are essentially extending life for not-very-long periods and sometimes the metastatic lesions are very hard to stop.

What we learned from looking at the timeline of cancer progression in the clinic is that before patients develop metastatic disease, in many cases, they can spend many years free of symptomatic disease before these lesions appear. Then, [we had] some basic questions on why cancer cells throughout the body that we [expected] to perpetually grow somehow stop. [We realized] there's an opportunity there, that we [could] target [the cells] in that state right before they start growing again to try to prevent those metastases.

The strongest need [is] to prevent and treat metastatic disease, and that impacts many cancers. Many types of presentations, [such as] brain metastases, liver metastases, lung metastases, [and] bone metastases, are all very hard to treat; some are harder than others. If we were able to understand how those metastases are initiated and try to capture them earlier, that would be a benefit.

What we learned from exploring this biology is that the cells do not seem to be doing the same things that they do when they're growing as a tumor lesion, either as a primary site or secondary site. They're shifting to this slow proliferation or sometimes very long periods of time where they remain ‘sleeping.’ Sleeping is a good metaphor because they are active, but they are not really engaging in growth. All their systems are still going just in a different mode.

Therapies that target dividing cells are ignored by these sleeping cells because they turn on mechanisms that are evolutionarily conserved to survive during these sleeping periods; this is not an invention of cancer. Organisms do it across evolution; they pause their development to survive and then, eventually, when things [improve] in their environment, they wake up and continue with their development. Cancer does the same. When [the cells] go into sleeping mode, they activate survival mechanisms that make them very sturdy; this is in addition to the fact that they are not dividing, and the therapies we use commonly target dividing cells.

[We want] to capture metastases early and prevent them. [We also know that there is] coexistence of sleeping cells with active metastasis, so if we had therapies that treat the growing metastases, or another therapy that kills these dormant cells, we would eliminate all the possible initiators of that relapse or a secondary relapse. In a nutshell, that is the rationale of why we went all in on this biology. We believe that we can change outcomes quite significantly.

What are some of your plans for your first year in your new role?

The [Albert Einstein] Institute has a vision to look at the biology of residual disease from a multidisciplinary angle. All patients are different, and they are exposed during their life to different variables, [such as] diet, aging, and background. We do not [yet] understand how all of these variables control the fate of the cancer that is left behind after initial treatment is completed.

We know that some signals can awaken these dormant cells, we just do not know exactly when they kick in, to [allow us to] read them and try to prevent the awakening of those cells. We want to take a multidisciplinary approach to understand how the immune system interacts with these dormant cells and how other components of the patient [interact with] these residual dormant cells and different organs. [Therefore], we need specialists from different backgrounds that understand the brain, the liver, and the bone; [having experts from] all these specialties [involved] is essential. [The new institute] will take a multidisciplinary approach to understand that biology in all these different contexts.

In the first year, we want to work toward recruiting scientists who are aligned with this vision of understanding the biology of dormancy, the biology of metastasis, and understanding how variables relate to inflammation, aging, and lifestyle choices. The idea is to bring new scientists who are not represented or who will complement existing expertise at Einstein to allow us to [look] at these questions from different angles. [We also want] to pair recruitment with the expertise that is already at Einstein, [with respect to] different aspects of immunology, stem cell biology, and importantly, technologies. Einstein has a great tradition of being good at developing tools and technologies to [address] biological questions.

My recruitment is associated with my role as co-director of the Gruss-Lipper Biophotonics Center, which is an amazing international resource for intravital imaging and pairing imaging with other technologies. The idea is to take advantage of this technology to see how we can [use] these methods and tools to [answer] these questions about dormancy and get a better insight into the mechanisms [involved].

In the first year [to] 2 years, the idea is to build a faculty that will be structuring questions for this biology. This is the first institute ever dedicated to this problem. Immediately, we will position it as a knowledge source and a [source] of information for other institutions, governments, patients, advocates to connect with us and learn from what we are [investigating]. It is a strong institute for Einstein and for the cancer research community.

Could you expand on the areas of unmet need that these efforts seek to address?

The biggest unmet need is the biology of metastasis. The incidence of metastasis and aggressiveness of the disease varies with [characteristics, such as] race, lifestyle, choices, and diet. We want to understand, for example, why African Americans may have more aggressive breast cancer progression than other ethnic groups. [Or], why some ethnic groups seem to have more mild disease. This can be asked in a mechanistic way and Einstein and its community and [connection] to Montefiore will allow us to explore these questions that have never really been explored.

There is also an issue of lifestyle choices, like diet, and how they impact [the] body. [Lifestyle choices like] what we eat, or whether we smoke, or whether we exercise, affect all these organs where the cells are sleeping. [We need to understand] how [these variables] will affect their ability to awaken. These are unmet needs that we have not addressed mechanistically and from the research point of view. They are [on] everyone’s radar in some way because we understand that these variables may impact how the cells behave.

The liver is a very good example; a significant proportion of the population in the United States and in Western cultures have fatty liver. The liver can accumulate fat, [which] starts to affect how it works. [The liver] can become inflamed [or] fibrotic, and all these are risk factors for liver cancer. We are also wondering whether they may be the risk factors, for example, for melanoma, breast cancer, gastric cancer, that spread to the liver and may not have started growing yet. Maybe over time, these factors tell these cancer cells to start growing again. We want to understand what the cancer is doing, but also what the host is doing to allow for these metastases to grow. This is something that has not been explored carefully and I believe we have an opportunity to do so now.

What is your take-home message for your colleagues?

We need to look at cancer as a disease that is more of a systemic problem; it doesn't [occur] only in the organ that the cancer is first detected in. Although this happens [in some cases], in many cancers, the disease really touches all corners of the patient's body. We need to understand that systemic relationship more carefully. My goal is to educate others on how to take the knowledge of this biology and bring it to the clinic. We are very used to doing things the same way in the clinic and it's our job as researchers to try to educate ourselves, the doctors, the advocates, and the patients [on] the options that research brings to us to open new avenues. [The options] may not be conventional but they could be effective.

Is there anything else that you would like to add?

We [want] create an institute that is diverse in its composition and diverse in its thinking, one that will integrate existing knowledge [and a] diversity of knowledge and cultures that is present at Einstein. I'm a believer that our culture, diversity, and our training come together in how we approach problems.

This is a difficult problem, so we need smart people who bring all their expertise, [including] their life experience and their training, to address these problems. We hope that we can bring this new energy and focus and impact other areas of Einstein Montefiore in the community.