Nature Reviews Cancer - Targeting cancer pathways

Targeting cancer pathways

Tumour formation and progression occur through a range of defects that develop both within and outside the cancer cell. Defects in cell-signalling pathways allow cancer cells to alter their normal programmes of proliferation, transcription, growth, migration, differentiation and death. Changes in the surrounding stroma and immune response allow the tumour to expand, form new blood vessels and spread to other organs. Many different anticancer agents have therefore been developed to target proteins that act in all of these pathways. Several agents – both small-molecule inhibitors and monoclonal antibodies (mAbs) – are on the market, and many more are in clinical trials or at earlier stages of development. The combined use of these inhibitors with standard anticancer treatments could allow researchers to attack tumours on many fronts.


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	Supported by an unrestricted educational grant from Novartis Oncology Combining the productivity of research scientists at facilities in the United States and Switzerland and the contributions of our commercial partners, Novartis Oncology is conducting a programme directed toward understanding the basic mechanism of malignancy from uncontrolled cell growth to angiogenesis and metastasis. The goal is to produce innovative new medicines that will extend and enhance the life of patients and improve the management of all types of cancer, particularly haematological cancers and cancers affecting the lung, breast, gastrointestinal and urogenital tracts. Compounds in the Novartis pipeline encompass innovative platforms that target multiple pathways. For example, ongoing research efforts target growth-factor signal transduction to impact tumour-cell growth and apoptosis. This includes investigation into two tyrosine-kinase inhibitors: one, which is in Phase I development, targets EGFR, HER2 and VEGFR, whereas the other agent, which targets FLT3, is in Phase II trials. Phase III research is being conducted with an anti-angiogenesis agent that blocks tumour vascularization to prevent tumour growth and metastasis and targets all VEGFR tyrosine kinases. Therapies are also being investigated in the cytotoxic and cell-cycle/apoptosis platforms to inhibit aberrant genetic processes that are responsible for malignant transformation. Research in cytotoxics includes Phase II trials that are being conducted into a microtubule-stabilizing agent and in an inhibitor of the enzyme topoisomerase I, while one other microtubule stabilizer is in Phase I development. Meanwhile, inhibitors of the mTOR kinase pathway and an inhibitor of histone deacetylase are in Phase II and Phase I trials, respectively. By approaching oncology research from these multiple fronts, Novartis Oncology hopes to optimize the future treatment of patients with cancer. For further information, please consult http://www.novartis.com Contact Geoff Cook Novartis Oncology Tel: +1 862 778 2675 geoffrey.cook@novartis.com ONC-9529