- Email: [email protected]
Quid pro Quo: A Tumor is Not Alone
TRMOME 1231 No. of Pages 2
[48_TD$IF]Special Issue: Cancer and the Organism
Editorial
Quid pro Quo: A Tumor is Not Alone Catarina Sacristán* and David A. Tuveson* In research as well as in the clinic, the view of cancer in relation to its host organism is evolving. Progressively, cancer is being viewed not as a single disease, but rather as a pathological state comprising a more complex set of problems in an organism’s physiology; namely, that a malignant tumor exerts effects on the organism just as the organism’s physiology exerts effects on the tumor. [49_TD$IF]Indeed, the body’s responses to the tumor may be beneficial (e.g., immune defenses) and/or detrimental (e.g., inflammation), but even then, in a context-, tissue-, cancer-, and individual-specific response, these effects might lead to opposite outcomes. It is the sum of all events that will determine a specific disease outcome for a given individual, principally molded by both genetic and environmental factors. A set of looming questions thus emerge[50_TD$IF]: might we arrive at a point where we can predict – to a certain extent – the outcome of a subset of malignancies, or the response to a therapeutic treatment, if and when we hold a better understanding of specific physiologic [51_TD$IF]states? Can we gain insight on the reciprocal interplay between the tumor and the host? What does the tumor give and what does the host give back (or vice versa)? Furthermore, what are some of the technological tools and advances that will enable us to address these queries? Our themed issue on ‘Cancer and the Organism’ reveals novel findings and discusses the molecular details of some of these questions. With the advent of new concepts and methodologies in the fields of cancer, inflammation, and immunity, the collection explores experimental approaches geared towards gaining mechanistic insight into tumor–host interactions and defense, aiming to provide avenues for a more accurate dissection of oncogenesis, progression, and treatment in a ‘physiological’ context. We begin our special issue with two spotlight articles showcasing exciting new research: Gary Doherty, Emma Kerr, and Carla Martins highlight mouse and human cell work describing how allelic imbalances and [52_TD$IF]3oncogene dosage of Kras might impact tumor development and therapy; and Eric Pamer discusses a genomic study documenting how human-resident intestinal bacterial species in colonized mice function to modulate the host immune system. Because microbial diversity and microbiota–host interactions have been strongly implicated in cancer, the illustrated findings resonate well with our theme of reciprocity. An important concern in cancer disease is the relationship between metabolic changes and the tumor. Seher Balaban, Darren Saunders, and Andrew Hoy provide an overview of the heterogeneous tumor microenvironment and the mammary stroma and propose a model where reciprocal metabolic adaptation between stromal adipocytes and breast cancer cells might modulate proliferation, invasion, and therapeutic resistance. From the perspective of mammalian physiology, the degree to which antioxidation promotes or inhibits tumorigenesis has been a longstanding question. Examining this controversy, Iok In Christine Chio and David Tuveson provide a thorough biochemical outlook on redox biology
Trends in Molecular Medicine, Month Year, Vol. xx, No. yy
*Correspondence: [email protected] (C. Sacristán) and [email protected] (D.A. Tuveson).
http://dx.doi.org/10.1016/j.molmed.2017.03.007 © 2017 Elsevier Ltd. All rights reserved.
1
TRMOME 1231 No. of Pages 2
and discuss how alterations in reactive oxygen species dynamics can influence carcinogenesis and homeostasis. The collection includes updated information on emerging technological tools and therapeutic approaches in this fast-advancing field by going one step further, examining how these strategies could be applied not only to cancer–host interactions but also to other disease pathologies. 3D organoids are occupying an important research platform in the cancer field; Devanjali Dutta, Inha Heo, and Hans Clevers describe various facets of organoid technology and its specific use in animal and patient-derived models of cancer, hereditary diseases, and host cell–microorganism interactions. Focusing on cancer treatment strategies, ZeNan Chang and Yvonne Chen offer a comprehensive overview of chimeric antigen receptor (CAR)-T cell designs, describing the successes, obstacles, and emerging solutions of CAR-T cell models in cancer immunotherapy and beyond. We end our lineup with two articles highlighting altered homeostasis, metabolism, and antitumor immunity, placing particular focus on pancreatic cancer. Thomas Flint, Tobias Janowitz, and Douglas Fearon examine the complex relationship between cancer and cachexia – the fatal wasting syndrome – homing in on the alterations in liver metabolism during cachexia that might lead to suppressed antitumor immunity. Constantinos Zambirinis and George Miller present a panorama of dysfunctional homeostasis in pancreatic cancer, depicting a web of maladaptive and imbalanced responses in this condition, which include inflammation, fibrosis, and impaired immunity. It follows that tumors are not lonely ‘creatures’, and a heightened understanding of tumor–host crosstalk is evidently warranted. A plethora of questions flourish from previous laid-out queries, yet important research efforts are already here and exciting progress is just on the horizon. We hope you will enjoy this special issue, where we have assembled some of today’s trends and left some food for thought. Many thanks to all authors and reviewers for their contribution and insight, and our apologies to the many scientists whose work in the field we were unable to add to this collection. We also invite you to read Cell’s ‘Cancer: the Road Ahead’ February special issue and Cancer Cell’s ‘Tumor–Host Interaction’ March issue. We would love to hear from our readers: please send your comments to [email protected] or @TrendsMolecMed. Quid pro quo: we give to you and hope you give back too . . . keep reading!
2
Trends in Molecular Medicine, Month Year, Vol. xx, No. yy
[48_TD$IF]Special Issue: Cancer and the Organism
Editorial
Quid pro Quo: A Tumor is Not Alone Catarina Sacristán* and David A. Tuveson* In research as well as in the clinic, the view of cancer in relation to its host organism is evolving. Progressively, cancer is being viewed not as a single disease, but rather as a pathological state comprising a more complex set of problems in an organism’s physiology; namely, that a malignant tumor exerts effects on the organism just as the organism’s physiology exerts effects on the tumor. [49_TD$IF]Indeed, the body’s responses to the tumor may be beneficial (e.g., immune defenses) and/or detrimental (e.g., inflammation), but even then, in a context-, tissue-, cancer-, and individual-specific response, these effects might lead to opposite outcomes. It is the sum of all events that will determine a specific disease outcome for a given individual, principally molded by both genetic and environmental factors. A set of looming questions thus emerge[50_TD$IF]: might we arrive at a point where we can predict – to a certain extent – the outcome of a subset of malignancies, or the response to a therapeutic treatment, if and when we hold a better understanding of specific physiologic [51_TD$IF]states? Can we gain insight on the reciprocal interplay between the tumor and the host? What does the tumor give and what does the host give back (or vice versa)? Furthermore, what are some of the technological tools and advances that will enable us to address these queries? Our themed issue on ‘Cancer and the Organism’ reveals novel findings and discusses the molecular details of some of these questions. With the advent of new concepts and methodologies in the fields of cancer, inflammation, and immunity, the collection explores experimental approaches geared towards gaining mechanistic insight into tumor–host interactions and defense, aiming to provide avenues for a more accurate dissection of oncogenesis, progression, and treatment in a ‘physiological’ context. We begin our special issue with two spotlight articles showcasing exciting new research: Gary Doherty, Emma Kerr, and Carla Martins highlight mouse and human cell work describing how allelic imbalances and [52_TD$IF]3oncogene dosage of Kras might impact tumor development and therapy; and Eric Pamer discusses a genomic study documenting how human-resident intestinal bacterial species in colonized mice function to modulate the host immune system. Because microbial diversity and microbiota–host interactions have been strongly implicated in cancer, the illustrated findings resonate well with our theme of reciprocity. An important concern in cancer disease is the relationship between metabolic changes and the tumor. Seher Balaban, Darren Saunders, and Andrew Hoy provide an overview of the heterogeneous tumor microenvironment and the mammary stroma and propose a model where reciprocal metabolic adaptation between stromal adipocytes and breast cancer cells might modulate proliferation, invasion, and therapeutic resistance. From the perspective of mammalian physiology, the degree to which antioxidation promotes or inhibits tumorigenesis has been a longstanding question. Examining this controversy, Iok In Christine Chio and David Tuveson provide a thorough biochemical outlook on redox biology
Trends in Molecular Medicine, Month Year, Vol. xx, No. yy
*Correspondence: [email protected] (C. Sacristán) and [email protected] (D.A. Tuveson).
http://dx.doi.org/10.1016/j.molmed.2017.03.007 © 2017 Elsevier Ltd. All rights reserved.
1
TRMOME 1231 No. of Pages 2
and discuss how alterations in reactive oxygen species dynamics can influence carcinogenesis and homeostasis. The collection includes updated information on emerging technological tools and therapeutic approaches in this fast-advancing field by going one step further, examining how these strategies could be applied not only to cancer–host interactions but also to other disease pathologies. 3D organoids are occupying an important research platform in the cancer field; Devanjali Dutta, Inha Heo, and Hans Clevers describe various facets of organoid technology and its specific use in animal and patient-derived models of cancer, hereditary diseases, and host cell–microorganism interactions. Focusing on cancer treatment strategies, ZeNan Chang and Yvonne Chen offer a comprehensive overview of chimeric antigen receptor (CAR)-T cell designs, describing the successes, obstacles, and emerging solutions of CAR-T cell models in cancer immunotherapy and beyond. We end our lineup with two articles highlighting altered homeostasis, metabolism, and antitumor immunity, placing particular focus on pancreatic cancer. Thomas Flint, Tobias Janowitz, and Douglas Fearon examine the complex relationship between cancer and cachexia – the fatal wasting syndrome – homing in on the alterations in liver metabolism during cachexia that might lead to suppressed antitumor immunity. Constantinos Zambirinis and George Miller present a panorama of dysfunctional homeostasis in pancreatic cancer, depicting a web of maladaptive and imbalanced responses in this condition, which include inflammation, fibrosis, and impaired immunity. It follows that tumors are not lonely ‘creatures’, and a heightened understanding of tumor–host crosstalk is evidently warranted. A plethora of questions flourish from previous laid-out queries, yet important research efforts are already here and exciting progress is just on the horizon. We hope you will enjoy this special issue, where we have assembled some of today’s trends and left some food for thought. Many thanks to all authors and reviewers for their contribution and insight, and our apologies to the many scientists whose work in the field we were unable to add to this collection. We also invite you to read Cell’s ‘Cancer: the Road Ahead’ February special issue and Cancer Cell’s ‘Tumor–Host Interaction’ March issue. We would love to hear from our readers: please send your comments to [email protected] or @TrendsMolecMed. Quid pro quo: we give to you and hope you give back too . . . keep reading!
2
Trends in Molecular Medicine, Month Year, Vol. xx, No. yy