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Therapeutic Resistance in Cancer: Mechanisms, Insights and Progress

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Therapeutic resistance remains a persistent challenge for patients, physicians and researchers. In the clinical setting, therapeutic resistance can occur at the outset of treatment, or may be acquired after an initial clinical response. While resistance to classical cytotoxic treatments has been studied for ...

Therapeutic resistance remains a persistent challenge for patients, physicians and researchers. In the clinical setting, therapeutic resistance can occur at the outset of treatment, or may be acquired after an initial clinical response. While resistance to classical cytotoxic treatments has been studied for decades in various experimental models, few of the mechanisms or models of resistance have been clearly shown to play a decisive role in the clinical setting, and still fewer are amenable to manipulation to overcome resistance.

With the approval of many targeted ‘precision medicines’ for common malignancies such as breast, colorectal, and lung cancer, as well as lymphoma and leukemia, patients are now being tested for aberrations in specific molecular targets with the intent to direct treatment to patients that will obtain a predicted therapeutic benefit. However, even in selected patients, therapeutic resistance remains a predictable challenge. While mutations in the target itself may be a cause of resistance, there are many other contexts in which the target of a clinically effective therapy is known, and mutations of the target itself do not appear to play a role in the development of resistance. The multidimensionality of tumors, including tumor heterogeneity, epigenetic modifications, microenvironment and host factors are likely contributors to compensatory pathways that underlie the emergence of resistance.

New translational research approaches are contributing towards understanding mechanisms of resistance using patient biopsies obtained during treatment. This multidisciplinary research will provide insight into potential escape mechanisms, and requires the participation of patients, clinicians, interventional radiologists, pathologists, and basic researchers. The purpose of this volume is to create a comprehensive overview of the multidimensional nature of drug resistance, as demonstrated using integrated approaches and recent advances in genomics, RNomics and proteomics. We encourage our colleagues to contribute their findings and perspectives on therapeutic resistance, from in vitro models and mechanistic pathways to translational and clinical research, with a particular focus on targeted therapies.


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