Roche continues to target molecular causes of cancer
Roche Pharma Research and Early Development continues to build on its long and robust history in Oncology R&D. Based on new disease biology insights, the new Molecular Targeted Therapy discovery research group is dedicated to understanding potential vulnerabilities of tumours at the molecular level, in order to discover novel treatments.
Unlike cancer immunotherapy (CIT), which is designed to harness the body’s immune system to attack the tumour, the Molecular Targeted Therapy (MTT) group mainly focuses on targeting the tumour itself. Along with CIT, molecular targeted therapy holds promise for treating tumour types with unmet medical need.
Jim Bischoff, Head of Molecular Targeted Therapy Discovery Oncology, said it is an exciting time to be in oncology research. “Cancer immunotherapy, which was not mainstream even a few years ago, is hopefully becoming a foundation therapy for some tumour types”.
However, not all patients benefit from CIT. “We believe molecular targeted therapies will continue to have potential to complement and augment responses in cancer patients that are currently underserved.”
As scientists gain greater understanding about tumour biology it has become clear that cancer is divided into ever more specific subtypes that are defined not only by location in the body, but as well by the context of genomic alterations and how they relate to intrinsic signalling pathways that drive or maintain tumorigenesis and resistance to therapy. Jim said the MTT group, located at the Roche Innovation Center in Basel, hopes to benefit from this growing insight in the areas of targeted protein degradation and cancer cell signalling.
Benefitting from new technologies to discover novel targeted cancer approaches
Cells, explained Jim, have their own built-in “rubbish disposal” known as the ubiquitin/proteasome system, which naturally degrades and “discards” unnecessary proteins. The goal of targeted protein degradation is to hijack this innate process to selectively degrade proteins that spur or sustain tumour growth. He said Roche is partnering with C4 Therapeutics, a US-based biotech company that has developed a pioneering technology that uses drug-like small molecules to direct disease-relevant proteins to the ubiquitin/proteasome system where they are destroyed.
The MTT team is also focusing on the complex system of cellular communication called cancer cell signalling. “We will be looking at genetic relationships that are wired differently in tumour cells than in normal cells,” noted Jim. The aim is to understand how cancer cells use these pathways to survive, flourish and resist treatment, then design therapies that disrupt or disable these mechanisms.
A third area of MTT research embraces our expertise in cancer immunotherapy, a research area of high strategic interest to pRED and led by Pablo Umaña at the Roche Innovation Center Zurich. The MTT team will focus on signalling pathways in immune cells that can either exclusively or preferentially be targeted by small molecules. Roche’s Zurich-based CIT group is mainly dedicated to large molecule research, which targets proteins expressed on the surface of cells. Jim said MTT’s small molecule research allows Roche to expand its CIT portfolio by also exploring small molecule targets. “We can access targets inside the cell,” he said. “This opens up many more possibilities because we are not restricted to targets on the outside of cells.”
Added Jim, “Our expertise and track record built by our colleagues from CIT over many years provided us a great runway in this exciting and emerging area of cancer research and drug discovery.”
A personal view on molecular targeted therapy: an interview with Jim Bischoff
Jim Bischoff, Head of Molecular Targeted Therapy Discovery Oncology shares his personal insights on Roche in oncology, why he is excited about exploring new ways to attack tumours at the molecular level and what motivates him to come to work every day.
How does molecular targeted therapy match the overall oncology research strategy at Roche?
The overall oncology strategy at Roche is science-based, data-driven drug discovery that is focused on patient populations where there is a lack of therapeutic options. Our molecular targeted therapy research will reflect this patient-focused strategy. We are starting by looking at patient populations with the poorest survival rates and we will focus on the tumour types where there is the most unmet medical need. Small molecule research offers significant potential in tumour-targeted treatment. Ultimately, we want to deliver therapies for molecularly defined patient populations that add to a physician’s toolkit of targeted medicines against cancer.
What is most exciting about this emerging field?
There is a higher bar in cancer therapeutics than ever before. We are seeing new approaches and molecules that have shifted the treatment landscape from the traditional cytotoxic therapies. In the same way that cancer immunotherapy research is uncovering the role of the immune system in tumour maintenance, molecular targeted therapy offers an opportunity to attack tumours at the molecular level. The more we learn about the biology and adaptability of cancers, it is increasingly apparent that combination therapies of cancer immunotherapies and molecular target tumour therapies will play an important role in treatment. It is both exciting and rewarding to be involved in research that has the potential to discover important therapies.
What motivates you to come to work every day?
I lost my first wife to breast cancer. When you see someone go through chemotherapy and live with the day-to-day realities of cancer, it makes it much more real, more personal, and puts a great sense of urgency on what we are trying to do. It motivates me every day to be a drug hunter. In addition, I am also motivated by the people I work with. They are a fantastic group of top-notch scientists who are also deeply committed to our research. Each has their own personal story on how cancer has impacted them and/or their family and they bring their dedication and passion to bear every day.