According to University of Wisconsin-Madison professor Zachary Morris, the university has experts in nearly every area of a rising field of cancer research called theranostics.
Morris, a faculty member at the School of Medicine and Public Health and Chair of the Department of Oncology, leads the UW-Madison Initiative for Theranostics and Particle Therapy. He told The Daily Cardinal the theranostics field has quickly been gaining traction over the past decade, and UW-Madison is poised to be at the forefront.
A theranostic, the word a portmanteau of “therapeutic” and “diagnostic,” is a radiation treatment combining the advantages of chemotherapy and radiation therapy. Theranostics are radioactive drugs, often administered intravenously, that travel through the body and contain chemicals or proteins that selectively bind to cells in a cancerous tumor. The radioactivity from the drugs accumulates in and kills tumor cells.
For years, UW-Madison research across disciplines has pushed this potentially lifesaving technology forward.
What do theranostics do differently?
Typically, invasive or malignant cancer detection and treatment follows a similar process: after a tumor forms and is detected through patient-described symptoms or notable lumps, a biopsy is performed.
If doctors confirm malignancy, they attempt to remove the cancer through surgery and other types of therapy. These include radiation therapy, which targets X-ray beams into the tumor to kill it, or chemotherapy, which uses strong medicines that prevent cancerous cells from multiplying or disrupt their communication pathways to program their death.
Scientific advances have greatly improved the outlook of patients with malignant tumors; some patients with stage 4 tumors can now expect to live for years. These advances are crucially important — the number of cancer cases per year is expected to increase to 26 million by 2030.
But no cancer therapy is perfect. The chemicals in chemotherapy, often administered intravenously, can travel throughout the body, killing or damaging healthy cells and causing fatigue, anemia, infertility, vomiting or mouth sores in some patients. In the worst cases, chemotherapy can cause long-term damage in critical areas like the heart and lungs and can even lead to a second cancer.
Current forms of radiation therapy, which Morris said more than half of all cancer patients receive as part of their treatment, face similar challenges. The most common form of radiation therapy is called external beam radiation, where X-rays are directed into the body at the region of the tumor. The beams can be shaped to the tumor, but some imprecision will always occur. Nearby healthy cells are inevitably zapped and damaged to some extent, causing many of the same symptoms as chemotherapy though usually in a more localized region.
Theranostic treatments allow radiation to hit cells precisely from inside the body, and the drugs’ special binding qualities allow them to focus radiation on tumor cells while minimizing damage to healthy cells on their way to their target.
How do theranostics work?
A theranostic is composed of three components: a vector, a chelator and a linker. The vector binds to a specific receptor on a cancer cell; the chelator binds to a radioactive metal atom, or isotope; the linker connects the vector to the chelator.
“The vector will bind to the cancer cell, and it'll be linked to the chelator, which will bring along the isotope,” Morris said. “That isotope is going to undergo radioactive decay — it's going to break down, and when it does, it emits radiation. That radiation is what damages the cancer cell.”
The radiation emitted from a theranostic operates similarly to the X-rays in external beam radiation therapy to kill cancer cells. However, instead of requiring precise machine alignment to deliver radiation to the area of the tumor, the vector within the theranostic directs the radiation to where it needs to go because the vector selectively attaches to tumor cells, minimizing its interactions with other cells — a quality called molecular specificity.
“[In radiation therapy], the patient has to be positioned on a table very precisely so that the tumor is in the correct location, and then the radiation is delivered to that point in space,” Morris said. “Whereas with radiopharmaceuticals… biological or molecular targeting is employed to deliver radiation specifically to the cancer cell and not to the normal cells.”
If the theranostic does not find its target, the patient will excrete the drug, limiting its harm to other areas of the body.
Some theranostics have been engineered to attack not just cancerous cells in a tumor, but also the benign appendages within the tumor called the tumor stroma. Tumor stroma include cells like fibroblasts, which normally function to heal wounds but accumulate in massive numbers within cancerous tumors. Left unchecked, tumor stroma can facilitate cancerous growth despite being non-cancerous themselves.
Collaborations at UW
In June, UW-Madison hosted the UW Theranostics and Particle Therapy Symposium, a two-day event where field experts gave talks and held poster sessions on topics within the field.
Some UW-Madison researchers work to develop new vector molecules to lock onto more and varied types of tumor cells. Others focus on chelator and isotope research, searching for better ways to produce and bind a radioactive substance. Still others perform pre-clinical testing of theranostics, ensuring in a laboratory setting that a drug is selective to tumor cells or experimental trials, where a theranostic is introduced to cancer patients.
“On the whole spectrum from the discovery science to clinical delivery of theranostics, we have people at UW who are experts,” Morris said.
Outside of the human oncology department, UW-Madison’s Nuclear Engineering Department conducts research on the design of cyclotrons, or particle accelerators, that purify and isolate new radioactive isotopes. Medical physics and radiology professors at UW-Madison are also leaders in theranostics development.
Morris said he enjoys bringing new members of UW-Madison into the field of theranostics, and the “team science” at the university represents the type of approach necessary to eventually achieve a cure to cancer.
“Growing up, I had a strong family history of cancer, and there were a number of family members who went through cancer treatment,” Morris said. “That was my longstanding motivation to get into the field of cancer research… I really enjoy working here at the University of Wisconsin, where it's a very collaborative environment and we have great teams of researchers that work together to advance these approaches.”
The past, present and future of theranostics
In the early 1900s, hospitals started using radium as a cancer treatment. The first theranostic, radioiodine, was deployed to treat hyperthyroidism in the early 1940s. An isotope of radium, Radium-223, continues to function as a theranostics agent today, particularly to treat aggressive forms of prostate cancer.
“We've done [theranostics] for more than 100 years,” Morris said.
The word “theranostic” was first used in 1998 by a pharmaceutical consultant. The past decade saw a rapid expansion of interest and research into the treatment, driven by advances in both chemistry and nuclear medicine. Currently, the FDA has approved several theranostics for use in cancer treatment.
“There have been a couple of approvals of new theranostics in the last five years, and there's hope that there will be many more of those coming.” Morris said. “There's a lot of research going on in this field right now.”
But significant research remains before theranostics can become a widespread treatment. Different radiopharmaceuticals treat specific types of cancerous tumors, and Morris said many of those drugs are still in development. The number of drugs limits the types of cancers that can be treated with theranostics: currently only prostate cancer, thyroid cancer and certain types of neuroendocrine tumors have dedicated radiopharmaceuticals.
In addition to vector and chelator development, UW researchers are also studying the effects of different decay products of radioactive isotopes.
There are three decay products: alpha particles, beta particles and gamma rays. A gamma ray is similar to an X-ray, a beta particle is similar to an electron, and an alpha particle is a heavier form of radiation like a helium atom. An isotope of a theranostic could emit one or a combination of these forms of radiation to kill a cancer cell, but their effectiveness varies.
“If the field continues to grow, there's the potential that this is the type of treatment that could exist for almost every type of cancer eventually,” Morris said. “The more funding that we can attract to cancer research in general, the more quickly we're going to make progress.”
