Immunotherapeutic approaches and their combination with anti-angiogenetic treatment
The major challenge in battling the cancer problem is the fact that cancer is a collection of different, constantly evolving genetic diseases. During tumor development incipient cancer cells undergo a multistep mutational process, during which they acquire a set of genetic and/or epigenetic lesions, which ultimately result in the cancerous state. These mutations provide the cancer cell with a set of traits that have been termed the ‘hallmarks of cancer’ – potential for unlimited proliferation, mitogen-independence, escape from apoptotic signals, immune evasion, sustained angiogenesis, tissue invasion and ultimately metastasis (Hanahan and Weinberg, 2000). These cancer phenotypes are thought to be the consequence of gain of function of oncogenes or inactivation of tumor suppressor genes. Due to recent technological advances, such as next generation sequencing, we are beginning to understand the complex genetic changes that ultimately result in cancerous growth.
In our group we are applying chemical genetics and in vivo approaches to investigate the molecular mechanisms that control tumor angiogenesis and tumor cell proliferation. Herein, we seek to define genetically encrypted correlates of tumor angiogenesis and tumor cell proliferation that enables to decipher new molecular therapeutically tractable targets. Another focus of our group are immunotherapeutic approaches and their combination with anti-angiogenetic treatment. We employ cell culture and syngeneic, autochthonous and other mouse models of various cancers such as lung cancer, breast cancer, lymphoma and sarcoma to study treatment combinations and mechanisms of actions and resistance. In doing so, we particularly focus on the effects of various treatment algorithms on the hosts immune system to decipher potential synergies with novel immunotherapies. We also aim to understand why only a minority of patients with certain cancers such as lung cancer respond to immunotherapy and why those that do respond become resistant to it. In the long term we hope to use synergistic, mechanistically plausible combination treatments together with immunotherapy to overcome these problems and translate our findings into patient care.