Feb 4, World Cancer Day

What A Nobel Prize-Winner’s Research Means for Cancer Treatment

The synthesis of complex molecules was significantly simplified by Drs. Carolyn Bertozzi, Barry Sharpless, and Morten Meldal, who shared the 2022 Nobel Prize in Chemistry. The protégé of Dr. Bertozzi explains why her research is so crucial.

For significantly simplifying the synthesis of complex molecules, Drs. Carolyn Bertozzi, Barry Sharpless, and Morten Meldal shared the 2022 Nobel Prize in Chemistry in October. The invention of click chemistry, which enables the joining of small modular units with biomolecules, is attributed to Drs. Sharpless and Meldal. In order to develop the subject of bioorthogonal chemistry, which is defined as click reactions that take place within biological systems, Dr. Bertozzi advanced the click chemistry principles. Copper is a common catalyst used in click chemical processes, however because of its toxicity, it cannot be used around live cells. Dr. Bertozzi was able to alter molecules in living things without impairing typical cell processes by getting rid of copper.

Dr. Bertozzi

Dr. Bertozzi’s work has spawned the creation of several biopharma companies, including Palleon Pharmaceuticals( where I work) Thios Pharmaceuticals, Redwood Bioscience, Enable Biosciences, InterVenn Biosciences, Lycia Therapeutics, and Olilux Biosciences. Her groundbreaking scientific discoveries have contributed to new modalities for treating many serious diseases that affect millions of people.Dr. Bertozzi’ findings have significant implications for the treatment of cancer. There had been over 50 scientific papers published – the earliest ones dating back to the 1960s – that demonstrated a positive correlation between higher density of sialoglycans on the surfaces of tumor cells and worse clinical outcomes for cancer patients. However, the mechanism that protects these tumors from the body’s immune response to cancer was unknown. Using tools enabled by bioorthogonal chemistry, she demonstrated that sialoglycans – which are glycans that terminate with a sugar building block called sialic acid – are immunosuppressive in cancer.

Glycoimmunology

Dr. Bertozzi had discovered a glyco-immune checkpoint similar to the PD-1 checkpoint that may be targeted for drug development, shedding light on a crucial axis of immune regulation. Her work has sparked the development of the area of glyco-immunology, which examines how glycans control and guide the body’s immunological response. Drug research in glyco-immunology has the potential to result in innovative medicines for the treatment of cancer, inflammatory conditions, and other critical diseases.

The immunotherapy landscape has made significant progress over the last few years, with several effective treatments now approved and available to patients. Most options that use this approach stem from treatments targeting CTLA-4 and PD-1/PD-L1 pathways, a discovery which was also recognized with a Nobel Prize in 2018 for Dr. James Allison and Dr. Tasuka Honjo. Over the last decade, the FDA has approved several immune checkpoint inhibitors targeting these pathways, including atezolizumab (Tecentriq), durvalumab (Imfinzi), ipilimumab (Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo).Beyond checkpoint inhibitors, approaches including non-specific immunotherapies that support the immune system in destroying cancer cells, oncolytic virus therapy that utilizes viruses altered within labs to destroy cancer cells, T-cell therapies, and cancer vaccines have all been studied and garnered approvals from the FDA.

Click Chemistry

The revolutionary discoveries made by Dr. Bertozzi have the potential to make a substantial impact on the field of immunotherapy. The Royal Swedish Academy of Sciences said it best when it said, “Click chemistry and bioorthogonal reactions have brought chemistry into the era of functionalism. The greatest benefit to humanity is being provided by this. Treatment for major illnesses like cancer has come a long way, but there is still more to be done. Millions of people with cancer and other critical diseases, whose demands are not addressed by today’s medications, will now be able to benefit from the development of novel treatments thanks to Dr. Bertozzi’s efforts. With this innovative method of medicine development, I have high hopes for the future of patients.

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