By Laurent Levy

“The emperor of all maladies; the king of terrors.”

It might sound like a line from a Shakespearean tragedy, but these were the words an unnamed 19th-century surgeon used to describe the ravages of cancer. Two centuries later, oncologist Siddhartha Mukherjee borrowed the first part of the phrase as the title for “The Emperor of Maladies,” his Pulitzer Prize-winning biography about how our understanding of cancer has changed over the last 4,000 years.

In his book, Mukherjee acknowledged that while cancer research has come a long way over the last millennia, one in three women and one in two men will still develop cancer during their lifetime, and 25% of all American deaths will be attributed to “the king of terrors.”

Can the emperor be dethroned? Many oncologists have said we’re not likely to discover a “silver bullet” to curing cancer. This is because cancer isn’t just one disease — more than 100 distinct types exist, each with its own biology and gene mutations. The number of treatments is even more dizzying. In 2020 alone, 20 cancer drugs were approved by the Food and Drug Administration (FDA) to treat or detect different kinds of cancer, each with varying success.

It may prove difficult to cure all cancers. But what if a single therapy had the potential to rid the body of many of them, no matter their biological makeup, chemical composition, and other distinctions? This is precisely what Nanobiotix aims to do by developing a therapeutic approach to cancer treatment that isn’t based on the moving targets of biology or chemistry, but rather on physical principles within the cell. We design products at nanoscale to modulate these principles and deliver positive outcomes for patients.

Let’s take a closer look.

The Problem With Treating a Moving Target

Cancer is a moving target. Our prognosis depends not only on how the disease manifests itself but also on the available treatment options for each of those manifestations.

Conventional therapeutic approaches, such as surgery, chemotherapy, and radiotherapy (also called radiation therapy), have wildly different success rates depending on the type of cancer. Early stages of breast cancer, for example, are very treatable and survivable, while any stage of glioblastoma (a type of brain cancer) is often a death sentence no matter the treatment regimen.

In the last chapter of a PBS documentary based on “The Emperor of Maladies,” Mukherjee said, “The cancer cell is evolving, and we are evolving with it.” Many oncologists now believe that cancer is a spectrum of diseases — a treatment that works for one patient may not work for another. New therapies are often personalized, based on a person’s specific genes and disease. CAR T-cell therapy, for example, genetically modifies a patient’s own T-cells to attack their cancer.

Yet while personalization has created better outcomes for some patients, it is still largely dependent on the type of cancer. For instance, CAR T-cell therapy is only effective against certain types of blood cancers, and it is often used as a last resort after exhausting other treatment options. In other words, despite our greater understanding of cancer, we’re still chasing the same moving target.

Stripping Away the Complexities of Cancer

Cancer is extraordinarily complex and has layers upon layers of mutations. This means that tumors caused by the same type of cancer may manifest differently in two people. It also means that different types of cancer are substantively different from each other depending on where they grow in the body and which type of cells they affect.

Treatments based on biology and chemistry target specific cancers, but they don’t reveal the underlying principles based on physics that can potentially lead to the treatment of all types.

I never got into a career in science to “cure” cancer. I trained as a physicist and, at least initially, I approached cellular biology as a physics problem, which led to the invention of innovative potential cancer treatments that could be broadly applicable across solid tumor indications. What this meant was that rather than focus on the personalization of cancer treatment, I wanted to ask questions that focused on the fundamentals, thereby stripping away the complexities of cancer. For example: Can we make our cells behave differently using physical science? Can we design a nanoparticle that, unlike larger molecules, might cross barriers between cells and be used as an active agent or drug? And can we develop therapies using principles of nanophysics to impact human health around the world?

The Same Boiling Water That Softens the Potato Hardens the Egg

Nanobiotix’s team strongly believes that “yes” is the answer to my questions. Today, Nanobiotix is focused on the development of a potential first-in-class, solid tumor-agnostic, therapeutic combination-agnostic radioenhancer called NBTXR3.

This is a bit of a mouthful, so let’s break this down. First, what is a radioenhancer?

To understand a radioenhancer, we first need to discuss radiotherapy, a type of treatment where radiation is used to destroy cancer cells or prevent them from growing by damaging their DNA. Although radiation can be effective in treating cancer, it may also harm healthy tissue. This means that doses may be limited, and therefore less effective.

Composed of hafnium oxide nanoparticles, our radioenhancer is injected into solid tumors and then activated by radiotherapy. Once activated, it is designed to absorb up to nine times the energy from the radiotherapy, increasing the dose delivered within the tumor and causing significant tumor cell death without increasing the dose in surrounding healthy tissues. Moreover, recent research data suggests that our radioenhancer also may prime the immune system to attack the target tumor as well as metastatic tumors throughout the body.

There’s an old saying, “The same boiling water that softens the potato hardens the egg.” Because NBTXR3 is physical rather than biological or chemical, we believe that it should, in theory, be scalable across solid tumor types and be combined with any other anti-cancer therapy.

In 2019, NBTXR3 received its first European market approval for the treatment of locally advanced soft tissue sarcoma and is currently being evaluated across a wide range of solid tumors and therapeutic combinations, with a global phase III study in head and neck cancer expected to launch before the end of 2021. But we believe our radioenhancer is just getting started.

Although there is no silver bullet to curing cancer, there may be a silver lining. Because our nanophysics-based approach may strip away biological and chemical complexities, our product may revolutionize cancer treatment. Rather than a moving target, the “emperor of all kings” would become a sitting duck.