Metastasis is the final stage of cancer progression and is responsible for more than 90% of cancer related deaths, claiming millions of lives worldwide. The most formidable challenge in the treatment of metastatic cancer is the emergence of resistance to current therapies. Informed by clinical data and using functional in vivo and in vitro models our group seeks to understand the mechanistic determinants for cancer progression, defined by metastatic competence and resistance to therapies. Both rely on programs that ensure the cancer cells’ survival during periods of enhanced cellular stress, limited survival cues and attacks by the immune system. Although fascinating and clinically important, mechanistic insights into these programs are still lacking. Our ultimate goal is to enhance the efficacy of current anti-cancer therapies using combinatorial treatment regimens and find new therapeutic avenues to fight metastatic cancer.
The treatment of metastatic cancer has undergone a paradigm shift in the last couple of years. The identification of specific “driver mutations” in tumors holds the promise of tailored, mechanism-based treatment strategies, which are commonly referred to as ‘targeted therapies’. These new generations of targeted therapies can achieve tumor control for several months and have replaced unspecific cytotoxic chemotherapies for many cancer types. However, durable treatment responses are rare, due to the emergence of aggressive, drug-resistant clones that drive relapse and rapidly form new metastases (Figure 1, below). As a result, cure rates and long-term survival rates of metastatic patients treated with targeted therapies remain disappointingly low.
To better understand the clinical emergence of resistant cells our work focuses on the poorly understood events during tumor regression.