A fascinating talk about cancer drug discovery was given by Dr. William Pao, Head of Oncology Discovery and Translational Area (DTA) at Roche Pharmaceutical Research and Early Development (pRED) during the Sachs 16th Annual Biotech in Europe Forum.
He started to explain what is cancer, for us to gain more insights:
- cancer is a genetic disease: tumors can harbor over 400 somatic mutations
- cancer is heterogenous: there are more than 200 types of cancers and a single patient tumor displays intra and inter-tumoral heterogeneity
- cancer can metastasize: once spread, it is virually incurable. Metastatic cancer survival at 5 years is extremely low (between 4 and 28%)
Based on those considerations, treatment is becoming much more complex today with a blend of chemotherapy, targeted medicines and immunotherapies. A right combination could extend survival by several months.
But how to develop drugs with increased efficacy against the smart strategies used by the disease (such as tumor angiogenesis)? According to Dr. Pao, 3 elements are necessary:
- understanding disease biology as well as druggable targets in the complexity of cancer molecular pathways
- developing fit-for-purpose molecules allowing to create the right drug with the right format against the right target
- personalizing healthcare with the administration of the right drug to the right patient at the right time
Beyond a better understanding of the disease, using more than a single strategy to target the cancer:
- Host directed with cancer immunotherapy. This approach is particularly challenging as some patients do not respond to it (innate or acquired immune escape) and other patients may fully benefit with long term survival
- Tumor directed with targeted medicines
External innovation, collaborations and partnerships, is fully leveraged in order for Roche to complement existing capabilities in the field (immunotherapy examples: CuraDev, Pieris, BluePrint; targeted medicines: Tensha, C4Therapeutics).
As a conclusion, Roche is well positioned to address the cancer challenges and, since the beginning of innovative cancer treatments, the company has always been perceived as the leader of the therapeutic area.
Missing points in his talk were considerations of patient’s quality of life (extending life does not always go with good quality of life because of treatment’s side effects) and drug pricing (adding more and more drugs to the treatment cocktail costs a lot of financial resources, not only paid by the health insurance but also by the patient).
DNA methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors. www.enzymlogic.com. Work done with the molecular visualization VMD program developed at the University of Illinois: www.ks.uiuc.edu/Research/vmd/