INTRODUCTION
YALE JOURNAL OF BIOLOGY AND MEDICINE 88 (2015), pp.105-106.
A Multifaceted Battle Against Cancer Xiaoni Liua* and Caroline Reissb a
Department of Pathology and bDepartment of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut
Cancer is the second leading cause of death in the United States [1]. As of early 2014, there were approximately 14.5 million Americans living with a history of cancer. There are also 1.6 million new cases of cancer estimated to arise in 2015 [2]. While cancer is often generalized by the definition of abnormal cell growth and invasion, it is, in fact, a group of highly heterogeneous diseases. We commonly categorize cancer by the affected organ, such as the breast, lung, and prostate. At the molecular level, these cancers can be even further divided into sub-groups based on protein expression profile, which is critical for clinical diagnosis, treatment decision, and prognosis prediction. Different types of cancer vary significantly from each other in aspects such as epidemiology, pathogenic mechanism, clinical manifestation, and management. The result is an overwhelmingly complex group of diseases that have taken a huge toll on our society. Because of this, cancer has been a constant focus for disease research and therapeutic development for decades. More recently, there has also been an explosion of cancer research that focuses on areas such as cancer prevention, early detection, and clinical management. Nevertheless, we are still facing many hurdles in the fight against this group of devastating diseases. In this issue of the Yale Journal of Biology and Medicine, we selected several articles that focus on a wide range of interesting topics related to cancer. Jansen et al. review different risk factors and prevention strategies for pancreatic cancer (PC†). Because PC has a high mortality rate, personal risk assessment and prevention are critical strategies for combating the disease. The authors discuss potential risk factors for PC, such as smoking and obesity, and emphasize that a healthy lifestyle can reduce a person’s risk of developing the disease. In addition, Jansen et al. assess three genome-wide association studies that identified sets of single nucleotide polymorphisms (SNPs) associated with PC.
Also within the topic of cancer prevention, DiMaio focuses on cervical cancer, one of the leading causes of death among women. Since the majority of the cervical cancer cases are caused by human papillomavirus (HPV) infection, the author discusses how HPV vaccines have the potential to prevent almost all future cases of the disease. Furthermore, we present an article by Tiwari and Bhargava, who provide a detailed review of the Fourier transform infrared (FTIR) spectroscopic imaging technique. Before a treatment plan is put in place for a cancer patient, biopsies are generally performed to evaluate the type and severity of the disease. FTIR is one of the emerging methods to analyze cells from a biopsy. FTIR requires very minimal sample preparation, does not require contrast agents, and is amenable to computational analysis, unlike conventional staining methods. The authors introduce the potential of using FTIR in digital diagnosis to assist pathologists in increasing accuracy of diagnosis. They also discuss practical considerations that ahould be made when implementing a modified FTIR protocol. New types of cancer therapies are constantly being investigated and implemented. One actively developing cancer therapy exploits synthetic lethality. Cancerous cells often contain specific mutations resulting in activated proto-oncogenes and/or inactivated tumor suppressors. These mutations create new synthetic lethal partners that are not present in normal cells. Thompson et al. provide a thorough review on studies that identify synthetic lethal partners for common cancerous mutations using chemical, siRNA, shRNA, and CRISPR library screens, as well as the DAISY approach. In a clinical review focusing on brain metastases by Colaco et al., the authors begin by introducing a medical case of a female non-small cell lung cancer patient who eventually developed brain metastases. The article follows the clinical progression of her disease and provides
*To whom all correspondence should be addressed: Xiaoni Liu, Department of Pathology, Yale University, 310 Cedar St., New Haven, CT 06520; Tele: 203-785-2759; Email: [email protected].
†Abbreviations: PC, pancreatic cancer; SNPs, single nucleotide polymorphisms; FTIR, Fourier transform infrared; HPV, human papillomavirus; BCC, basal cell carcinoma. Copyright © 2015
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an insightful discussion on various treatment modalities in the management of brain metastases. Kuntsman and Longo profile the life and career of Dr. Ashley W. Oughterson, Professor of Surgery at Yale University. The article describes Dr. Oughterson’s contribution and dedication in promoting surgical therapy for gastrointestinal malignancies. He published several case reports showing that patients who underwent surgery for their cancer had higher long-term survival rates. In a case report by Jhaveri et al., the authors describe a medical case of a young female patient with Li-Fraumeni Syndrome and multiple malignancies with a de novo mutation in TP53. The authors discuss the benefits and risks over intensive cancer screening and shed light on what the best clinical management for this disease could be. We also present an interesting analytical study by Maroongroge et al., which investigates the cost of cancer-related physician services in Part B Medicare. The authors discuss how the trending shift in reimbursements for cancer care may reflect a change in clinical management. Marzuka et al. provide a comprehensive review of basal cell carcinoma (BCC), a type of skin cancer. While BCC is rarely deadly, it is one of the single most common types of cancer. The review covers topics in BCC pathogenesis, epidemiology, clinical manifestation, diagnosis, histopathology, and management. Also related to skin cancer, Liu interviews Dr. Harriet Kluger, Professor of Medicine and Associate Director of the Hematology/Oncology Fellowship Program at Yale University. Dr. Kluger speaks about the recent successful clinical trial using combination immune therapy in treating advanced melanoma patients. Moreover, Dr. Kluger shares with us her thoughts
on the current challenges in conducting cancer-related clinical trials. The conversation also touches on her dual role as a practicing medical oncologist and a cancer research scientist. Cancer represents a family of diseases that is highly heterogeneous and adaptive. To emphasize the multidisciplinary approach that is applied and the vast array of challenges that persist in the battle against cancer, the manuscripts in this issue address a broad range of topics, including molecular mechanisms of cancer pathogenesis, clinical diagnosis and management, epidemiology, and cancer-related health policies. Currently, much research is focused on identifying, characterizing, and exploiting heterogeneity in cancer cells at the level of protein expression. At the physician level, there are cancer type-specific concerns regarding the benefits of constant screening and aggressive therapy for preventive and disease management purposes, respectively. Translational research efforts, which lie at the interface between the bench and the bedside, will be critical in combating this overwhelmingly complex group of diseases. Overall, we hope that this issue provides insight into the remaining challenges in our war against cancer. REFERENCES
1. Leading Causes of Death. Centers for Disease Control and Prevention [Internet]. [cited 2015 May 12]. Available from: http://www.cdc.gov/nchs/fastats/leading-causes-ofdeath.htm. 2. Cancer Facts & Figures 2015. American Cancer Society [Internet]. [cited 2015 May 12]. Available from: http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/.
YALE JOURNAL OF BIOLOGY AND MEDICINE 88 (2015), pp.105-106.
A Multifaceted Battle Against Cancer Xiaoni Liua* and Caroline Reissb a
Department of Pathology and bDepartment of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut
Cancer is the second leading cause of death in the United States [1]. As of early 2014, there were approximately 14.5 million Americans living with a history of cancer. There are also 1.6 million new cases of cancer estimated to arise in 2015 [2]. While cancer is often generalized by the definition of abnormal cell growth and invasion, it is, in fact, a group of highly heterogeneous diseases. We commonly categorize cancer by the affected organ, such as the breast, lung, and prostate. At the molecular level, these cancers can be even further divided into sub-groups based on protein expression profile, which is critical for clinical diagnosis, treatment decision, and prognosis prediction. Different types of cancer vary significantly from each other in aspects such as epidemiology, pathogenic mechanism, clinical manifestation, and management. The result is an overwhelmingly complex group of diseases that have taken a huge toll on our society. Because of this, cancer has been a constant focus for disease research and therapeutic development for decades. More recently, there has also been an explosion of cancer research that focuses on areas such as cancer prevention, early detection, and clinical management. Nevertheless, we are still facing many hurdles in the fight against this group of devastating diseases. In this issue of the Yale Journal of Biology and Medicine, we selected several articles that focus on a wide range of interesting topics related to cancer. Jansen et al. review different risk factors and prevention strategies for pancreatic cancer (PC†). Because PC has a high mortality rate, personal risk assessment and prevention are critical strategies for combating the disease. The authors discuss potential risk factors for PC, such as smoking and obesity, and emphasize that a healthy lifestyle can reduce a person’s risk of developing the disease. In addition, Jansen et al. assess three genome-wide association studies that identified sets of single nucleotide polymorphisms (SNPs) associated with PC.
Also within the topic of cancer prevention, DiMaio focuses on cervical cancer, one of the leading causes of death among women. Since the majority of the cervical cancer cases are caused by human papillomavirus (HPV) infection, the author discusses how HPV vaccines have the potential to prevent almost all future cases of the disease. Furthermore, we present an article by Tiwari and Bhargava, who provide a detailed review of the Fourier transform infrared (FTIR) spectroscopic imaging technique. Before a treatment plan is put in place for a cancer patient, biopsies are generally performed to evaluate the type and severity of the disease. FTIR is one of the emerging methods to analyze cells from a biopsy. FTIR requires very minimal sample preparation, does not require contrast agents, and is amenable to computational analysis, unlike conventional staining methods. The authors introduce the potential of using FTIR in digital diagnosis to assist pathologists in increasing accuracy of diagnosis. They also discuss practical considerations that ahould be made when implementing a modified FTIR protocol. New types of cancer therapies are constantly being investigated and implemented. One actively developing cancer therapy exploits synthetic lethality. Cancerous cells often contain specific mutations resulting in activated proto-oncogenes and/or inactivated tumor suppressors. These mutations create new synthetic lethal partners that are not present in normal cells. Thompson et al. provide a thorough review on studies that identify synthetic lethal partners for common cancerous mutations using chemical, siRNA, shRNA, and CRISPR library screens, as well as the DAISY approach. In a clinical review focusing on brain metastases by Colaco et al., the authors begin by introducing a medical case of a female non-small cell lung cancer patient who eventually developed brain metastases. The article follows the clinical progression of her disease and provides
*To whom all correspondence should be addressed: Xiaoni Liu, Department of Pathology, Yale University, 310 Cedar St., New Haven, CT 06520; Tele: 203-785-2759; Email: [email protected].
†Abbreviations: PC, pancreatic cancer; SNPs, single nucleotide polymorphisms; FTIR, Fourier transform infrared; HPV, human papillomavirus; BCC, basal cell carcinoma. Copyright © 2015
105
106
Liu and Reiss: Introduction
an insightful discussion on various treatment modalities in the management of brain metastases. Kuntsman and Longo profile the life and career of Dr. Ashley W. Oughterson, Professor of Surgery at Yale University. The article describes Dr. Oughterson’s contribution and dedication in promoting surgical therapy for gastrointestinal malignancies. He published several case reports showing that patients who underwent surgery for their cancer had higher long-term survival rates. In a case report by Jhaveri et al., the authors describe a medical case of a young female patient with Li-Fraumeni Syndrome and multiple malignancies with a de novo mutation in TP53. The authors discuss the benefits and risks over intensive cancer screening and shed light on what the best clinical management for this disease could be. We also present an interesting analytical study by Maroongroge et al., which investigates the cost of cancer-related physician services in Part B Medicare. The authors discuss how the trending shift in reimbursements for cancer care may reflect a change in clinical management. Marzuka et al. provide a comprehensive review of basal cell carcinoma (BCC), a type of skin cancer. While BCC is rarely deadly, it is one of the single most common types of cancer. The review covers topics in BCC pathogenesis, epidemiology, clinical manifestation, diagnosis, histopathology, and management. Also related to skin cancer, Liu interviews Dr. Harriet Kluger, Professor of Medicine and Associate Director of the Hematology/Oncology Fellowship Program at Yale University. Dr. Kluger speaks about the recent successful clinical trial using combination immune therapy in treating advanced melanoma patients. Moreover, Dr. Kluger shares with us her thoughts
on the current challenges in conducting cancer-related clinical trials. The conversation also touches on her dual role as a practicing medical oncologist and a cancer research scientist. Cancer represents a family of diseases that is highly heterogeneous and adaptive. To emphasize the multidisciplinary approach that is applied and the vast array of challenges that persist in the battle against cancer, the manuscripts in this issue address a broad range of topics, including molecular mechanisms of cancer pathogenesis, clinical diagnosis and management, epidemiology, and cancer-related health policies. Currently, much research is focused on identifying, characterizing, and exploiting heterogeneity in cancer cells at the level of protein expression. At the physician level, there are cancer type-specific concerns regarding the benefits of constant screening and aggressive therapy for preventive and disease management purposes, respectively. Translational research efforts, which lie at the interface between the bench and the bedside, will be critical in combating this overwhelmingly complex group of diseases. Overall, we hope that this issue provides insight into the remaining challenges in our war against cancer. REFERENCES
1. Leading Causes of Death. Centers for Disease Control and Prevention [Internet]. [cited 2015 May 12]. Available from: http://www.cdc.gov/nchs/fastats/leading-causes-ofdeath.htm. 2. Cancer Facts & Figures 2015. American Cancer Society [Internet]. [cited 2015 May 12]. Available from: http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/.
