Over the years, there have been a number of significant advances in the treatment and management of cancer.
However, cancer has been, and continues to be, one of the most challenging diseases to solve. Despite decades of research dedicated to the search for cures, cancer is currently the world’s biggest killer, responsible for the deaths of around 10 million people globally, young and old, every year. For this reason, there is a need to explore new ideas and new concepts.
With 18 million new cases of cancer worldwide reported in 2020, and 10 million deaths, there is a need to explore new ideas and new concepts.
Cancer is caused by faults, called mutations, in the DNA of cancer cells that causes them to grow uncontrollably. These cancer cells have a frustrating capability to outsmart attack by our immune system, the first line of defence. In addition, response to chemotherapy and targeted therapy is frequently not long-lasting due to the development of resistance. To add further fuel to the fire, because of the large variety of different mutations, a treatment that works for one individual might not have the same result in another. Because of this complexity, scientists across the globe are searching for different approaches to target cancer in new ways.
One of the new approaches being applied by scientists is to precisely target a vulnerability of cancer cells. This includes important concepts such as synthetical and collateral lethality, whereby DNA mutations found in cancer cells render them highly sensitive to precision cancer treatments. A potential advantage of this approach is maximising the effects of the drug against cancer cells whilst sparing normal tissues. Challenges include identifying the right cancers, which often requires the development of new assays based on genomics or protein expression.
Having overseen the development of many new cancer drugs across a career in pharma and biotech spanning close to 30 years, Brian Schwartz was in search of a company pursuing science that no-one has applied. In 2022, he joined Step Pharma as its CMO. Brian and the team at Step Pharma are homing in their efforts on targeting an enzyme called cytidine triphosphate synthase (CTPS) 1.
But why is CTPS1 so important?
Dividing cancer cells require a continual supply of nucleotides to replicate their DNA. Pyrimidines, one of the essential classes of nucleotide, are supplied by the de novo pyrimidine synthesis pathway. Every step in this pathway is catalysed by a single enzyme, except the final step where two enzymes, CTPS1 and CTPS2, can catalyse the conversion of UTP to CTP. Recent studies have shown that cancer cells are addicted to CTPS1 in order to keep dividing, whereas CTPS2 is sufficient for the proliferation of healthy cells. This is why the Step Pharma team believes that selectively targeting CTPS1 is so important.
“What gets me up in the morning is working for a company that is trailblazing a new journey to improve outcomes for those living with cancer. Our concept selectively targets an Achilles’ heel of cancer cells which we hope will stop cancer in its tracks.”
Brian Schwartz, CMO, Step Pharma
Targeting the key pathways on which cancer cells depend has the potential to improve outcomes for those living with cancer. In addition, the development of highly selective drugs has the potential to decrease unwanted effects on normal cells. The net result is treatments that are more effective at killing cancer cells but with fewer unwanted side effects.
“Whilst the ultimate wish of those living with cancer is to be cured of their disease, freedom from treatment associated side effects is also very important. Through the development of highly selective drugs targeting key cancer pathways, we are aiming to improve both survival and quality of life.”
Brian Schwartz, CMO, Step Pharma