Therapy’s Shadow: A Short History of the Study of Resistance to Cancer Chemotherapy

Abstract

This article traces the history of research on resistance to drug therapy in oncology using scientometric techniques and qualitative analysis. Using co-citation analysis, we generate maps to visualize subdomains in resistance research in two time periods, 1975–1990 and 1995–2010. These maps reveal two historical trends in resistance research: first, a shift in focus from generic mechanisms of resistance to chemotherapy to a focus on resistance to targeted therapies and molecular mechanisms of oncogenesis; and second, a movement away from an almost exclusive reliance on animal and cell models and toward the generation of knowledge about resistance through clinical trial work. A close reading of highly cited articles within each subdomain cluster reveals specific points of transition from one regime to the other, in particular the failure of several promising theories of resistance to be translated into clinical insights and the emergence of interest in resistance to a new generation of targeted agents such as imatinib and trastuzumab. We argue that the study of resistance in the oncology field has thus become more integrated with research into cancer therapy – rather than constituting it as a separate domain of study, as it has done in the past, contemporary research treats resistance as the flip side to treatment, as therapy’s shadow.

β-caryophyllene enhances the transcriptional upregulation of cholesterol biosynthesis in breast cancer cells

“…Even though these were not the most sensitive to BCP, we chose to analyze UFH-001cells because targeted therapies for TNBC patients are not available. Because hypoxia is the environment associated with aggressive breast cancers, and an independent prognosticator for poor patient outcome [34], we also chose the condition of hypoxia to evaluate the effect of BCP. In addition, we extended the exposure time from 4 h ( Figure 2) to 16 h ( Figure 3) to allow for transcriptional responses.…”

The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

“…An important player involved in the failure of treatment in cancer is the resistance against chemotherapy known as multidrug resistance (MDR). It is a phenomenon that has been receiving great attention in the last 50 years [6,7] due to the sheer amount of mechanisms discovered and involved in the process of resistance which hinders the effectiveness of many anti-cancer drugs [8][9][10][11][12][13]. It is a challenge that needs to be further investigated and overcome and is a paramount factor in cancer recurrence and low survival rates [14][15][16][17]…”

Resistance Development: A Major Piece in the Jigsaw Puzzle of Tumor Size Modeling

“…The advent of the genomics era and the subsequent introduction of targeted cancer therapies, accompanied by the technological development and adoptions of new clinical measurement tools and approaches, have tremendously influenced the research on therapy resistance. The investigation of underlying mechanisms responsible for resistance appearance reveals a historical evolution in the level of complexity at which specific molecular pathways have been studied . Moreover, in addition to the knowledge derived from preclinical systems, the recognition of clinical trials as pivotal in generating new information unveils the need for considering resistance as an essential part of the therapy and of the clinical efficacy evaluation.…”

“…The investigation of underlying mechanisms responsible for resistance appearance reveals a historical evolution in the level of complexity at which specific molecular pathways have been studied. 1 Moreover, in addition to the knowledge derived from preclinical systems, the recognition of clinical trials as pivotal in generating new information unveils the need for considering resistance as an essential part of the therapy and of the clinical efficacy evaluation.…”