Moonshots at Cancer: The Roche Story

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Abstract

This book tells the story of Hoffmann LaRoche’s engagement with oncology from the 1950s to circa 2010, using the Roche story as a case study for the role of industry in the search for chemical and biological cancer medicines.

Cancer medicine at Roche began with 5-fluorouracil (short: 5-FU), a drug which underwent first clinical tests in 1956 and was approved by the Food and Drug Administration (FDA) for ‘the chemical treatment of cancer’ in the United States in 1962. 5-FU was soon followed by a second Roche chemotherapy drug, procarbazine, which interferes with cell division by binding to DNA. Procarbazine was marketed as Natulan in Europe and Matulane in the US. The drug was first tested clinically in 1964 and received FDA approval in 1969.

Both 5-FU and Natulan were included in pioneering combination chemotherapy regimens developed by clinical researchers at the US National Cancer Institute (NCI) in the 1960s, which demonstrated that some cancers could indeed be cured by way of chemotherapy. 5-FU is a direct precursor of Xeloda (capecitabine), which was developed at Roche’s research centre in Kamakura, Japan, approved for medical use in 1998, and is still part of Roche’s current oncology portfolio.

In 1986, Roferon A, a form of interferon was approved for the treatment of hairy cell lymphoma and Kaposi sarcoma, one of the first of a completely new type of biological agents, a protein molecule produced using a new biotechnological method, which mediated a response of the immune system against viruses and cancer. Roferon A was a product of much research in molecular biology, including at two research institutes funded by Roche, and the application of innovative biotechnological approaches. It transformed Roche’s approach to drug development well beyond oncology.

The cloning of interferon was the first project in which Roche collaborated with Genentech, a pioneering biotech company based in San Francisco. In 1990, Roche purchased 60 percent of Genentech’s shares, and in 2008 the remaining shares it did not own.

The next generation of cancer drugs were developed wholly or in part by Genentech scientists, and marketed by Genentech in the US and Roche in the rest of the world. Trastuzumab (Herceptin), rituximab (MabThera/Rituxan) and bevacizumab (Avastin) are biotechnologically re-engineered monoclonal antibodies.

Trastuzumab, marketed as Herceptin and first approved by the FDA for the treatment of advanced breast cancer in 1998 selectively binds to a protein known as a growth factor receptor. The receptor which trastuzumab blocks is particularly common on the surfaces of cancer cells in about 30 percent of breast cancer patients whose tumours test positive for a cancer gene, a so-called oncogene, known as HER2/neu.

Rituximab, marketed in Europe as MabThera and in the US as Rituxan, and first approved in 1997 for the treatment of non-Hodgkin’s lymphoma, a cancer of the immune system, specifically binds to B-cells, a type of immune cell that turns malignant in this disease. Rituximab was developed jointly with a San Diego-based biotech company, IDEC, and first approved in 1997.

Bevacizumab (brand name: Avastin) docks to VEGF, vascular epidermal growth factor, a protein that controls the development of blood vessels in a process known as angiogenesis, and by doing so stops blood vessels from growing into tumour tissues, thus depriving the tumour cells of oxygen and nutrients. It was first approved for the treatment of advanced colorectal (bowel) cancer in 2004.

Erlotinib, finally, marketed as Tarceva and also approved in 2004, for advanced lung cancer, is not a monoclonal antibody. Developed initially by another small biotech firm, OSI Pharmaceuticals, it is not a protein but a small molecule, much like traditional chemotherapy drugs, but it specifically blocks a receptor for Epidermal Growth Factor, EGRF.

The book aims to bring an industry perspective to the story of modern cancer science, which has often been told without this perspective in mind, as a series of government initiatives and Eureka moments. In the 1950s and 1960s, cancer chemotherapy research was dominated by government agencies and above all the National Cancer Institute in the US, which managed and funded drug screening programmes and clinical trials. At that stage, no pharmaceutical company made much money with cancer drugs. The role of industry changed in the 1970s and 1980s, when investments in molecular biology and biotechnology were starting to bear fruit, and chemotherapy was increasingly accepted as a valuable part of routine cancer treatment, complementing the two older treatment modalities, surgery and radiotherapy. Increasingly more research was initiated and financed by industry: fundamental, technological and clinical, to accommodate new molecular approaches and more complex production methods, and to respond to regulatory requirements.

Bibliographical metadata

Original languageEnglish
Place of PublicationBasel
PublisherEditiones Roche
Number of pages154
ISBN (Print)978-3-907770-96-2
Publication statusPublished - 2020

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