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From next-generation “living drugs” to ultra-precise radiation to taking on targets once thought to be “undruggable,” we’re pursuing technologies we believe have potential to make a true difference in patients’ lives.

For most of human history, our options for treating cancer were limited to three pillars: surgery, radiation, and chemotherapy. A little over two decades ago, a fourth pillar emerged. Targeted therapies ushered in an era of precision oncology by honing in on unique molecular changes that drive the formation and spread of cancerous cells. Cancer, however, is not a single disease. It’s more than a hundred diseases with diverse causes and characteristics, which happen to share a common feature — abnormal cells that grow out of control. Tremendous progress has been made in treating many of these types and subtypes of cancer, but an urgent need for new and better treatments remains.

At Novartis, we are pursuing technologies we believe have the potential to make a true difference in patients’ lives — technologies that could become new pillars for cancer treatment long into the future. Here are three we’re especially excited about.

1. T-Charging into the future

When it comes to cancer, the word “cure” can be controversial. But in recent years and in certain contexts, it’s becoming harder to avoid. For example, the results of a decade-long study recently highlighted the potential of immuno-oncology, an approach that uses patients’ own immune systems to fight cancer.

The study followed patients treated a decade ago with then-experimental CAR-T therapy, a treatment for certain blood cancers that sits at the intersection of cell-, gene-, and immuno-based therapies. Scientists extracted immune cells called T cells from the patients, and genetically engineered them in a lab to recognize and destroy cancer cells. These modified T cells were then put back into the patients’ bodies, where they acted as a “living drug.” As of February 2022, when the study was published, the modified T cells were still patrolling and no signs of the patients’ cancer were detectable.

There is still a lot of work left to be done to make CAR-T better and more effective, so that it could potentially benefit more patients. One of the main challenges has been the time it takes to extract T cells and engineer them in a lab — time that is of the essence for patients. This is why Novartis scientists innovated T-ChargeTM. The T-Charge process dramatically shortens the time it takes to genetically engineer T cells, so they can be given back to patients faster. T-Charge also helps T cells retain “stem-like” properties, meaning these cells primarily expand within the patient’s body and persist in patients longer — hopefully giving the cells a better chance to control cancer. We’re currently studying T-Charge in clinical trials to better and more precisely gauge its potential efficacy.

2. Meet the New Radiation

Radiation is one of the oldest pillars of cancer treatment. By focusing destructive beams of energy onto tumors, doctors can often destroy or even eradicate cancer cells. This process, however, causes unwanted collateral damage. What if we could use radiation to destroy cancer cells in a targeted way? And what if we could better predict which patients might benefit from such a treatment? These questions are central to a new technology called radioligand therapy.

Radioligand therapy uses special molecules that bind to specific receptors expressed in high amounts by certain cancers. Once given to a patient, these molecules circulate throughout the bloodstream, attaching to target cells, including cancer cells anywhere they may be in the body. Connected to each molecule is a therapeutic radioisotope — an atom that emits a tiny amount of radiation. When a cancer cell is exposed to enough radioisotopes, the combined radiation can damage and destroy it, while limiting damage to cells that don’t express the receptor.

An alternative radioisotope can also be used specifically for imaging. This allows doctors to see where the molecules travel and if they concentrate in tumors, giving powerful insight into where the tumors are, and which patients might benefit from treatment — a true “treat what you see” approach to oncology. As patients advance through the course of radioligand therapy, doctors are also able to use this imaging capability to evaluate the impact of treatment — so they “see what they treat.” Radioligand therapy is currently used for certain neuroendocrine tumors and some prostate cancers, and Novartis scientists are diligently working to apply it to many other types of cancer.

3. To dream the undruggable dream

Targeted therapies have cemented their place in cancer treatment. However, a fundamental challenge remains. Many proteins that can drive cancer, including a major group called transcription factors, don’t have the molecular properties needed for scientists to develop targeted therapies using classic medicinal chemistry approaches. Such proteins are essentially untouchable — or “undruggable.” Unfortunately, the majority of known cancer-driving proteins fall into this category.

But our scientists are rising to the challenge. They are leveraging a technology platform called targeted protein degradation, which takes advantage of the cell’s native “trash disposal system” — the proteasome, a piece of internal machinery for eliminating unwanted proteins. The approach involves creating compounds that glue a special chemical tag called ubiquitin onto proteins of interest. This tag signals to the cell that the tagged proteins should be disposed of by the proteasome.

With targeted protein degradation, scientists have the ability to remove cancer-driving proteins from the cell, rather than just blocking their activity. It may also allow for fine control over the amount of protein inside a cell, enabling therapies that control protein expression as if it is on a dimmer switch, instead of a binary on-off. Targeted protein degradation is still in its early stages, but Novartis scientists are dedicated to realizing its potential for patients — and to someday eliminating the word “undruggable” from the oncology lexicon for good.

Hear from our researchers below on why they’re personally excited about these technologies. And learn more about our areas of research and opportunities to join our scientific teams.