Innovation Is the Answer to Making Progress Against Cancer

In recognition of her innovation and empowerment, Shanta Dhar, PhD, FRSC, was named a fellow of the National Academy of Inventors for her ongoing research on combination therapeutic nanoparticles in prostate cancer.¹

Dhar is an associate professor of biochemistry and molecular biology and the assistant director of technology and innovation at the Sylvester Comprehensive Cancer Center’s NanoTherapeutics Research Laboratory, in Miami, Florida. The announcement was made in December 2023.

Dhar joins Nobel Prize laureates and National Inventors Hall of Fame inductees, as well as National Academies of Sciences, Engineering, and Medicine members, in the 2023 class. The academy plans to recognize Dhar and the other fellows during an induction ceremony slated for June 18, 2024.

In an interview with Oncology Fellows, Dhar discussed the significance of this honor and dove into the focus of her research in mitochondrial nanomedicine and the development of prodrugs with modulated mechanisms of action.

Oncology Fellows: You were recently named a fellow of the National Academy of Inventors. Congratulations! What is the personal significance of this appointment to you?

Dhar: It’s an honor to be inducted as a fellow of the National Academy of Inventors, particularly this year with this incredible list of people. Some of them are my mentors!

To be a fellow of the National Academy of Inventors shows the appreciation of what we do day-to-day in our research toward innovation. I often tell my students, “Innovation: You often don’t see it. You have to feel it.” To be recognized as a fellow solidifies the aspect that innovation is important and that the work we are doing in the lab is innovative. I’m telling my students to keep being innovative and to start from a place where it looks like nothing is possible and then build on that.

What is your research focus and its potential clinical impact?

[I have] a background in chemistry and targeted drug delivery, and we started thinking about how we can make targeted drug delivery a platform technology so that it can be applied to many diseases or different types of cancer. The mitochondria play a significant role in many diseases and in cancer now that we know more metabolic aspects. [Thus,] mitochondria are a standout as one of the targets to develop subplatform technologies.

[However,] getting to the mitochondria is very challenging. In our lab we started working on how we can get things to the mitochondria of cells with a nanotechnology platform, particularly polymeric nanoparticles which can be degraded in the body and are more biodegradable and biocompatible, and can be fine-tuned for how fast or how slow the drug is released and how many drugs you can load in.

In the context of different types of cancer we look at the pathways that are either overexpressed or altered in particular types of cancer. Once we know what mitochondrial target we have, then we develop molecules that can work on the pathway. We are developing this as a platform, using that same nanoparticle we have used from the beginning to get to the mitochondria, to then turn on and turn off particular pathways.

[In terms of] clinical impact, these kinds of nanotechnologies are so new; [however,] all these recently approved vaccines, such as the COVID-19 vaccines, have nano components. Therefore, we feel that nano medicine is no longer foreign. However, the regulations for nano medicine, particularly for cancer, are still being developed. One challenge in the field is how to scale up this technology so that you can make off-the-shelf medicine. We are working very closely with clinicians to do work on that clinical aspect. We have been able to validate targets in clinical samples, and potentially we are looking at putting something in a real translational path.

Could you expand on the potential impact of developing nanoparticle technology for prostate cancer?

I have been working in prostate cancer for a long time. When I was a fellow at Massachusetts Institute of Technology [MIT], we developed different targeted nanoparticles that can get to the prostate cancer. [We worked on] developing polymers where you can load multiple drugs, which then can be released in a spatial temporal manner, meaning that in a particular area, 1 drug will release faster or another [will release] slower and you can have this control.

When I started my lab back in 2010, the first-ever grant we received was a prostate cancer idea award from the Department of Defense that led us to develop this combination therapeutic nanoparticle for prostate cancer. Once I moved to The University of Miami, we received a research grant to work on this prostate cancer research from the Florida Department of Health. Within that pathway, we developed this particular molecule, which looks like shards of the fat metabolism in prostate cancer, which appears to particularly happen in advanced cancer.

However, fat metabolism also happens in the liver, so this kind of therapeutic needs to be targeted. We developed an orally administrable nanoparticle, which is targeted to prostate cancer, and we now have the ability to deliver this compound orally [for patients with this disease].

We are looking at how this can be combined with other kinds of therapy, whether you can also supplement this kind of nanoparticle with another nanoparticle, which will then prevent bone metastasis, which is one of the sites where prostate cancer metastases. Then, we are trying to find additional pathways that happen in advanced prostate cancer. We continue to design molecules and synthesize molecules to target those pathways.

What made you want to pursue this innovation in oncology? Where does your passion come from?

I realized the potential when I was in MIT. I worked with people who were my mentors and were great innovators. MIT celebrates innovation; [it is a place that empowers you to believe] nothing is wrong, you can ask any question, and you can do anything—and that drove the process.

I understood how to file a patent because I had a lot of responsibility and freedom to do things [including] how to write a patent and how to work with a lawyer to get things filed. From some of my postdoc work, we were able to do a start-up and that gave me the push I needed. When I was an assistant professor in Georgia, I was able to put patents in very quickly because of that background and was able to launch my own start-up.

We ended up running the company for a few years and received some venture funds. The focus has always been the innovation and the ability to make molecules and create new chemical entities; that is probably the core to all this innovation. I have been very lucky to have my trainees.

What are you looking forward to most as you join the National Academy of Inventors?

[I plan to] be very practical. Everyone has limited funds, and universities also have limited funds for filing patents. We are all competing for funds to propel our [research] forward. I hope that Sylvester Comprehensive Cancer Center and the University of Miami file all my ideas that I’m putting forward.

I’m looking forward to all the upcoming meetings to interact with [people in the academy] to get to know them more, celebrate innovation, and keep pushing the research forward in this dimension. I’m [also] coleading an effort here with [The University of Miami’s] College of Engineering called Engineering Cancer Cures, where we are forming teams of cancer researchers and engineers to solve problems.

For example, if you want to look at pancreatic cancer more closely where models are not available, can an engineer work on an [inexpensive] model and you look at the biology? These are very big ideas we are working on. I want to have a lot of focus in that area to promote more innovation here at Sylvester Comprehensive Cancer Center beyond my lab.

Reference

Sylvester cancer researcher and technology innovator named fellow of the National Academy of Inventors. News release. Sylvester Comprehensive Cancer Center. December 18, 2023. Accessed January 25, 2024. https://www. newswise.com/articles/sylvester-cancer-researcher-and-technology-innovatornamed- fellow-of-the-national-academy-of-inventors?channel=