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Therapeutic resistance in cancer
Societal challenge
Cancer presents an urgent societal challenge. It takes 9.6 million lives each year, 90% of which result from untreatable cancer relapse occurring after initially effective treatment. Therapeutic resistance is one of the primary causes of cancer death and is clinically difficult to predict, prevent or treat. The plasticity of tumours that counteracts therapeutic intervention and gives rise to therapeutic resistance has been explored from many different angles in recent decades. However, there is no comprehensive understanding of the underlying resistance mechanisms, nor how they differ between cancer types or therapies. A better understanding of these mechanisms can contribute to better patient stratification, the development of effective drug strategies targeting the resistance mechanisms and the design of better cancer drugs.
Industrial challenge
Therapeutic resistance is a major industrial challenge since it causes failure in the drug discovery and development process. Therapeutic resistance is a process which is unpredictable and difficult to model. Therefore, better tools are needed to identify or predict resistance mechanisms. This would, in turn, decrease the costs and risks associated with cancer drug development significantly. Importantly, solutions to prevent or target therapeutic resistance will enhance the development of new therapeutics and market opportunities.
Experimental and scientific challenge
Current experimental approaches fail to study residual disease, the major cause of cancer relapse, and therapeutic resistance in clinically meaningful ways. In the last years novel single-cell sequencing has seen significant advancements. Such techniques combined with advanced cancer modelling approaches can shed light on the intricate processes underlying therapeutic resistance and residual disease. Understanding the mechanisms of cancer resistance is crucial to enable its mitigation and requires a coordinated effort.
Mechanisms of therapeutic resistance
Scientists have observed a number of mechanisms underlying drug resistance. These can be categorized as either intrinsic (present in the cancer cells independent of treatment outset of cancer treatment) or acquired (occurring as a consequence of the treatment). Initially, researchers believed that therapeutic resistance is primarily intrinsic in nature, caused by genetic traits in certain pre-existing cancer cells. In contrast, scientists have recently estimated that up to 50% of drug resistant cancer stems from acquired resistance mechanisms. This discovery presents an opportunity: a shift in focus from treating cancer spread mechanisms to preventing therapeutic resistance. This shift can have significant impact on the lasting effectiveness of cancer treatment and the life expectancy for cancer patients.