Cancer is a worldwide health burden and represents a major public health challenge in Europe. It is responsible for 25% of all deaths, being the second most common cause of death after cardio-vascular diseases and the main cause of mortality among people aged 45–64. Today, an estimated 9 million individuals in Europe live with cancer (Globocan 2008, http://globocan.iarc.fr/). Cancer became a chronic disease which contributed substantially to the growth of medical expenditures and constitutes a major socio-economic challenge for Europe as well as globally. A rapid and effective bidirectional transfer of relevant cancer research findings between bench and bedside would play a pivotal role in addressing top-priority needs at the EU level to reduce incidence and mortality of malignancies and to improve the quality of life of cancer patients. The proposed ERA-NET Cofund TRANSCAN-2, in continuity with the preceding and ongoing TRANSCAN ERA-NET, aims at linking translational cancer research funding programmes in 15 Member States, 3 Associated Countries, and a third country. By concentrating transnational resources, TRANSCAN-2 will provide a critical financial and scientific mass for tackling large-scale problems, relevant for improving translational cancer research globally. A co-funded joint transnational call (JTC) will be launched focusing on the topic “Intratumour heterogeneity in resistance to therapy and recurrence” followed by three additional JTCs that will be implemented in a frame of multinational translational cancer research programmes. In addition, strategies will be developed for the enlargement of the network, for improvement of coordination and for an efficient communication and dissemination of the results of the consortium as well as of the research projects funded through the JTCs. The monitoring of the projects funded through the JTCs and the critical assessment of the performance of TRANSCAN-2, based on key indicators, will be also realised.