bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Hallmarks of Cancer
Authors: Hanahan Douglas , Weinberg Robert A.
Published: August 2023

Overview

An enigma for cancer medicine lies in its complexity and variability, at all levels of consideration. The hallmarks of cancer constitute an organizing principle that provides a conceptual basis for distilling the complexity of this disease in order to better understand it in its diverse presentations. This conceptualization involves eight biological capabilities—the hallmarks of cancer—acquired by cancer cells during the long process of tumor development and malignant progression. Two characteristic traits of cancer cells facilitate the acquisition of these functional capabilities. The eight distinct hallmarks consist of sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics and metabolism, and avoiding immune destruction. The principal facilitators of their acquisition are genome instability with consequent gene mutation and tumor‐promoting inflammation. The integration of these hallmark capabilities involves heterotypic interactions among multiple cell types populating the “tumor microenvironment” (TME), which is composed of cancer cells and a tumor‐associated stroma, including three prominent classes of recruited support cells—angiogenic vascular cells (AVC), various subtypes of fibroblasts, and infiltrating immune cells (IIC). In addition, the neoplastic cells populating individual tumors are themselves typically heterogeneous, in that cancer cells can assume a variety of distinctive phenotypic states and undergo genetic diversification during tumor progression. Accordingly, the hallmarks of cancer—this set of necessarily acquired capabilities and their facilitators—constitute a useful heuristic tool for elucidating mechanistic bases and commonalties underlying the pathogenesis of diverse forms of human cancer, with potential applications to cancer therapy.
Oncogenes
Authors: Pierotti Marco A. , Frattini Milo , Molinari Francesca , Sozzi Gabriella , Croce Carlo M.
Published: August 2023

Overview

The initiation and progression of human neoplastic diseases is a multistep process involving the accumulation of genetic changes in somatic cells. These genetic changes typically consist of the activation of cooperating oncogenes and the inactivation of tumor suppressor genes, which both appear necessary for a complete neoplastic phenotype. Oncogenes are altered versions of normal cellular genes called proto‐oncogenes, usually involved in the regulation of cell growth and activated by mutation, chromosomal rearrangement, or gene amplification. In this chapter, at first we will describe the methods that have been applied by the researchers for the discovery and the identification of oncogenes. Then we will present the genetic mechanisms of proto‐oncogenes activation (point mutations, gene amplifications, chromosomal rearrangements) with several examples, and we will describe the role played by oncogenes in the initiation and progression of various cancers.

The identification of oncogene abnormalities has provided tools for the molecular diagnosis and monitoring of cancer. Most important, oncogenes represent potential targets for new types of cancer therapies, which are continuously discovered and tested in clinical trials. The goal of these new drugs is to kill cancer cells selectively while sparing normal cells. These new therapies display an evident benefit for the treatment of several neoplastic diseases that were, before targeted therapies development, very hard to be treated and cured. However, they are not able to kill 100% of neoplastic cells, essentially due to the occurrence of mechanisms of secondary resistance. In the last part of the chapter, we will review all the genes for which a targeted therapy has been developed.
Tumor Suppressor Genes
Authors: Cosgrove David , Park Ben Ho , Vogelstein Bert
Published: August 2023

Overview

Cancer is a genetic disease. Mutations and other alterations in growth promoting genes (oncogenes) and tumor suppressor genes can accumulate during the lifetime of a normal cell resulting in cancer. Unlike oncogenes, tumor suppressor genes generally require biallelic inactivation in order to demonstrate a cancerous phenotype. Importantly, the discovery of heritable tumor suppressor gene mutations that lead to familial forms of cancer has revealed great insight into tumor suppressor function. This has clinical screening implications for individuals with a family history of cancer and has led to newer therapies to target cancer cells with loss of specific tumor suppressors.
Epigenetic Contributions to Human Cancer
Authors: Herman James G. , Baylin Stephen B.
Published: August 2023

Overview

Over the past 20 years, an exciting advance in our understanding of the mechanisms underlying cancer development has been our growing appreciation that these diseases are not driven solely by genetic changes, but also by epigenetic changes.1–4Strictly speaking, the term epigenetic refers to heritable changes in gene expression, in dividing somatic cells, which are mediated by alterations other than changes in the primary base sequence of DNA.5–7This definition encompasses two critical translational characteristics concerning epigenetic alterations in cancer and their clinical importance. First, the coding and noncoding genes affected by epigenetic changes in cancer remain wild type for DNA sequence rather than harboring irreversible mutations. Second, and closely related, the changes are, then, potentially reversible if normal gene expression can be restored such that the wild‐type gene function can emerge.1,2,4,7–10

This recognition of epigenetic changes, which are fundamental to cancer initiation and progression, is occurring in the midst of a dynamic explosion of knowledge as to how the human genome is normally controlled, via chromatin packaging of DNA, to regulate gene expression in different tissues and during development.5–7,11For example, epigenetic processes play a fundamental role during normal embryonic development and adult‐cell renewal. As such, these processes control the emergence of different cellular phenotypes, all with the exact underlying DNA sequence, which occur during development and differentiation. While this knowledge of gene regulation continues to grow rapidly, our understanding of the complete spectrum of epigenetic changes that are key to cancer development is expanding rapidly but could even still, relatively, be in its early stages. However, there is much that has already been learned, and this knowledge in the understanding of basic cancer biology and carcinogenesis already has palpable translational implications, which are discussed in this chapter.
Differentiation Therapy
Authors: Chen Sai‐Juan , Yan Xiao‐Jing , Zhou Guang‐Biao , Chen Zhu
Published: August 2023

Overview

Abnormal differentiation is one of the main features of human cancers, especially in hematological malignancies. Many aberrant genetic and epigenetic factors have been shown to disrupt the regulation of cell differentiation in a variety of cancers and play an important role in oncogenesis. Differentiation therapy refers to the application of therapeutic agents selectively targeting the key molecules involved in the process of cell differentiation, leading to the restoration of normal cellular homeostasis and the eventual clearance of cancer cells. Over the past four decades, investigations of the molecular mechanisms underlying cancer cell differentiation arrest or blockage have allowed the identification of an array of drug targets. On the other hand, many physiological or pharmacological agents have been tested usingin vitroandin vivosystems as the inducers of differentiation and maturation of cancer cells. The translational research in this field has gradually turned the differentiation therapy from a concept to clinical practices. The most successful model of cancer differentiation therapy is the development of synergistic targeted treatment of acute promyelocytic leukemia (APL) with all‐trans‐retinoic acid (ATRA) and arsenic trioxide (ATO). This chapter discusses the basic theories of differentiation therapy and the clinical achievements of this therapeutic approach.
Modeling Therapy of Late or Early‐Stage Metastatic Disease in Mice
Authors: Kerbel Robert S. , Paez‐Ribes Marta , Man Shan , Xu Ping , Guerin Eric , Cruz‐Munoz William , Ebos John M. L.
Published: August 2023

Overview

An ongoing problem in oncology drug development is the frequent failure of preclinical therapy models involving treatment of tumor‐bearing mice, which show positive results, to predict similar success in patients enrolled in clinical trials. There are numerous possible reasons for causing such high rates of false positives. One is the failure to reproduce the clinical circumstances of treating systemic metastatic disease, whether microscopic or macroscopic in nature—but especially the latter. Thus, it is still common practice to treat mice with established primary tumors, whether they are transplanted or spontaneous, of mouse or human origin, or derived from cell lines or tumor tissue grafts—including human patient‐derived xenografts (PDXs). In this chapter, we summarize recent progress in developing mouse models of spontaneous metastases, especially of late‐stage disease, after surgical resection of primary tumors, including the use of human tumor cell lines, PDXs, and genetically engineered mouse models (GEMMs). Some limited therapy results using such models, and how they retrospectively or prospectively correlated with relevant phase III clinical trial outcomes, are discussed. A limited database indicates the possible benefits of using such models for predictive investigational therapeutic studies relevant to the treatment of patients with metastatic disease. Some limitations of such models are also discussed.
Chemical Carcinogenesis
Authors: Hofseth Lorne J. , Weston Ainsley , Harris Curtis C.
Published: August 2023

Overview

Human exposure to chemical carcinogens can result in cancer. What dictates this outcome is relatively predictable but highly variable. Factors governing the outcome include type of exposure, amount of exposure, time of exposure, and genetic makeup of the host (i.e., humans). The latter is comprised of variations in single nucleotides within genes (e.g., single nucleotide polymorphisms in deoxyribonucleic acid–repair genes), as well as the metabolomic, proteomic, microbiomic, transcriptomic, and epigenomic background of the individual. It is becoming increasingly clear that these endpoints can be modified by chemical carcinogens and that inflammatory load influences outcome. To this end, the past decade has seen an explosion of extremely sensitive and highly accurate technology. Linking this technology to the rapid development of bioinformatics has enabled us to begin merging the totality of lifetime exposure (exposome) with the totality of metabolomic, proteomic, microbiomic, transcriptomic, epigenomic, and other “omic” profiles. We feel optimistic that the next decade will bring the development of tools to identify an individual's weighted risk signature as a biomarker for cancer risk and develop a personalized and precise approach to cancer chemoprevention and treatment.
Endocrine and Genetic Bases of Hormone‐Related Cancers
Authors: Bernstein Leslie , Pu Xia , Gu Jian
Published: August 2023

Overview

Neoplasia of hormone‐responsive tissues currently accounts for more than 30% of all newly diagnosed male cancers and almost 40% of all newly diagnosed female cancers in the United States. Given that endogenous hormones apparently affect the risk of these cancers and their overall frequency, concern exists about the effects on cancer risk if the same or closely related hormones are administered for therapeutic purposes (e.g., as contraceptives, as menopausal hormone therapy, or for the prevention of miscarriage). Depending on the timing of hormone use and the tissue‐specific effects, some of these compounds will reduce risk while others increase risk of “hormone‐dependent” cancers. This chapter focuses on breast, endometrial, and ovarian cancers among women and prostate cancer among men and provides a review of the epidemiologic and endocrinologic evidence for the role of hormones in cancer development. It also reviews the current status of the relationship between exogenous hormones and risk of cancers of the breast, endometrium, and ovary. In addition, it summarizes our current knowledge of genetic susceptibility to breast, endometrial, ovarian, and prostate cancers. Other less common cancers (e.g., cervical cancer, clear cell vaginal adenocarcinoma, thyroid cancer, testicular cancer, and osteosarcoma) may have a hormonal basis as well, but are not reviewed in this chapter.
Inflammation and Cancer
Authors: Todoric Jelena , Umemura Atsushi , Taniguchi Koji , Karin Michael
Published: August 2023

Overview

Epidemiological studies and experimental evidence have provided strong support to the long standing notion that chronic inflammation stimulates the development and progression of malignant neoplasms. It is now clear that pre‐existing inflammation caused by persistent viral and microbial infections, autoimmune diseases, environmental irritants, and even obesity promote tumor development and may account for up to 20% of all cancer deaths. Inflammation also appears subsequent to cancer development and such “tumor‐elicited inflammation” plays a key role in the malignant progression and metastatic dissemination of most cancers. Although some common anti‐inflammatory drugs, such as aspirin, substantially reduce cancer risk, there is still an unmet need for the clinical development of new therapeutics that target cancer‐associated inflammation.
Palliative Care and Pain Management
Authors: Smith Cardinale B.
Published: August 2023

Overview

Palliative care is an essential component of comprehensive cancer care. Palliative care is given concurrently with other disease‐modifying, life‐prolonging, and curative therapy. Palliative medicine specialists focus on helping patients and their families with a variety of care needs including symptom control, psychosocial support, physician–patient communication, addressing care goals in relation to the patient's condition, prognosis, values, and preferences, as well as with transitions in care. Cancer patients often experience significant symptom distress either from the illness itself or from the associated treatments. The beneficial effects of palliative care have been well documented. When integrated into early oncologic care, palliative care is associated with a significant improvement in quality of life, depression, and survival. As such, palliative care should be given throughout the trajectory of cancer care whether during early stage disease in which the focus is on cure or in more advanced disease when the focus is on maximizing quality of life. Currently, national and international organizations have clinical guidelines that recommend palliative care be routinely integrated into comprehensive cancer care.
Personalized Medicine in Oncology Drug Development
Authors: Dracopoli Nicholas C. , Grewal Iqbal , Takimoto Chris H. , Lebowitz Peter F.
Published: August 2023

Overview

The concept of personalized medicine in oncology drug development is no longer an aspiration; it is now, in large measure, the accepted paradigm of how oncology drugs should be developed. In modern oncology drug development, determining which molecularly characterized tumors will benefit the most from a drug is a critical part of the development plan. In addition, another important personalized medicine approach is emerging whereby a therapeutic is specific to an individual patient. Examples of this individualized therapeutic approach include engineering of autologous immune cells with reinfusion into the patient or cancer vaccines that are specific to an individual tumor.

A growing number of successful examples have demonstrated that the personalized medicine approach via biomarker selection can provide more benefit to patients and more rapid approval of drugs. The benefits of a personalized medicine strategy in oncology drug development are multiple and include an increased probability of overall success, smaller Phase 3 registration trials, and the potential for enhanced clinical benefits for patients. In a recent review, Falconi and colleagues examined the outcome of 676 Phase 1, 2, and 3 clinical trials of novel therapeutics for non‐small cell lung cancer conducted from 1998 to 2012.1Overall, the cumulative success rate, as defined by the advancement to the next stage of clinical testing or to approval, was only 11%. However, when a biomarker was utilized for patient selection, the cumulative success rate increased by nearly sixfold to 62%. Thus, there is strong objective evidence for predictive biomarkers to enhance the probability of success in drug development. Using specific genetic and/or protein markers, a number of important drugs have been developed and approved in specific populations. This approach represents a paradigm shift that has proved so powerful that it is now a standard.
Pharmacology
Authors: Sharma Manish R. , Ratain Mark J.
Published: August 2023

Overview

The biology and clinical indications relevant to systemic anticancer therapies are covered extensively in other chapters in this book. In this chapter, we will focus on the principles of clinical pharmacology as they apply to systemic anticancer therapies and will attempt to illustrate how an understanding of clinical pharmacokinetics and pharmacodynamics can optimize the therapeutic index of these agents. The United States Food and Drug Administration (FDA) conducts a question‐based clinical pharmacology and biopharmaceutics review for each approved drug (http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffPoliciesandProcedures/ucm073007.pdf). Their reviews are publicly available on the FDA website (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/) by searching for the drug name, and often include details that are not included in the product label. We will use their standard questions to introduce the principles of clinical pharmacology and will highlight examples that illustrate these principles.
Carcinoma of the Stomach
Authors: Schmidt Carl , Murphy Mariela Blum , Yao James C. , Crane Christopher H.
Published: August 2023

Overview

Gastric cancer is the second most common cause of cancer‐related death worldwide and risk factors include autoimmune gastritis, chronic
Helicobacter pylori
infection, obesity, and other causes. Some countries with higher incidence have established screening programs but methodology and eligibility remain controversial. Despite knowledge of risk factors and screening for high‐risk populations, identification of earlier stage potentially curable disease remains a challenge.

Multiple genetic mutations are involved in gastric cancer pathogenesis, and mutations in the cellular adhesion protein CDH1 result in familial diffuse gastric cancer. Certain patterns of metastatic disease have been associated with particular molecular alterations. Increasing understanding of molecular pathways involved in gastric cancer has led to efficacious use of targeted biologic therapies with cytotoxic chemotherapy in the advanced setting, such as use of trastuzumab in patients with gastric cancer and
HER2/neu
overexpression.

Surgical resection is the primary potentially curative therapy in those without metastatic disease. Type of resection and extent of lymphadenectomy are not consistent, and standards for best practice are needed. Chemotherapy and radiation play an important role in the adjuvant setting and, therefore, decisions regarding choice and timing of these therapies require accurate staging by thorough evaluation with endoscopy, cross‐sectional imaging and, in some cases, endoscopic ultrasound or positron emission tomography.

Palliative interventions and therapy are often important, both for patients with symptoms in the metastatic setting and after recurrence as cure is not achieved in either situation. Results of recent clinical trials are encouraging, and there have been multiple positive phase III trials in the adjuvant and metastatic setting during the past 10 years. Despite this, most people diagnosed with gastric cancer will die from it eventually, so much more research is needed.
Primary Neoplasms of the Liver
Authors: Shindoh Junichi , Brudvik Kristoffer W. , Vauthey Jean‐Nicolas
Published: August 2023

Overview

Primary liver cancer is the second leading cause of cancer death in men and the sixth leading cause among women. Hepatocellular carcinoma (HCC) constitutes 70–85% of primary hepatic neoplasms, followed by intrahepatic cholangiocarcinoma (ICC) (10–15%) and other less common hepatic malignancies (5%) such as hepatic angiosarcoma, epithelioid hemangioendothelioma, or hepatic lymphoma. Primary hepatic malignancies are generally associated with poor survival, and only a limited evidence of systemic therapy have been available, prevention, surveillance, early diagnosis, and multidisciplinary treatment approach are important factors to maximize treatment outcomes. In addition, most of the primary hepatic neoplasms are associated with chronic liver disease or cirrhosis, and the decreased hepatic functional reserve often precludes aggressive treatment for tumors. Therefore, for treatment selection, one should consider two intrinsic conflicting factors, curability and safety of treatment. Currently, several clinical staging systems and treatment algorithms are available to adequately select therapeutic options for HCC. The choice of therapy is individualized based on the tumor burden, degree of underlying liver disease, patient performance status, and the overall possibility of side effects or complications balanced with acceptable results. Selection of treatment should be determined in a multidisciplinary approach with the local expertise. The most curative treatment options including surgical resection, radiofrequency ablation, and orthotopic liver transplantation (OLT) should be the first priority as long as such treatments are approved. For the other hepatic malignancies, only limited clinical evidence is available and surgical resection or OLT is considered as the first‐line treatment.
Gallbladder and Bile Duct Cancer
Authors: Kaseb Ahmed O. , Uemura Marc , Thomas Melanie B. , Curley Steven A.
Published: August 2023

Overview

Primary gallbladder and bile duct cancers are relatively rare tumors of the gastrointestinal tract. Both are mainly adenocarcinomas that start as abnormal growths within the mucous lining of the gallbladder and bile ducts. Bile duct tumors, or cholangiocarcinomas, are further differentiated by their location within the liver (intrahepatic) or outside the liver (extrahepatic). Both tumor types have distinct pathophysiologies and modes of hepatocarcinogenesis. Gallbladder cancers, for example, are associated with gallstones, chronic choleycystitis, and the porcelain gallbladder. They are commonly found incidentally on cholecystectomy specimens. On the other hand, cholangiocarcinomas have frequent associations with parasitic infections and other diseases causing chronic inflammation in the bile ducts (primary sclerosing cholangitis). While both gallbladder and cholangiocarcinomas can be cured if surgically resected, unresectable or advanced tumors have a poor prognosis and usually require systemic chemotherapy.
Neoplasms of the Anus
Authors: Minsky Bruce D. , Guillem Jose G.
Published: August 2023

Overview

Although an uncommon tumor, the incidence of anal cancer has increased over the past few decades. This increase may be due to sexual transmission of human papillomavirus virus as well as the impact of human immunodeficiency virus. Chemoradiation therapy (CMT) involving pelvic radiation and concurrent chemotherapy (5‐FU combined with either mitomycin‐C or cisplatin) has resulted in 5‐year survival rates of approximately 80% while maintaining sphincter preservation for most patients. Surgery is reserved for selected patients with T1M0 disease who can undergo resection with acceptable functional outcomes or an abdominoperineal resection (APR) for salvage following CMT.
Urothelial cancer
Authors: Raghavan Derek , Cote Richard , Burgess Earle F. , Riggs Stephen B. , Haake Michael
Published: August 2023

Overview

Urothelial malignancy is one of the most common cancers in Western society and involves the bladder, urethra, ureters, and renal calyces. It is predominantly associated with smoking, industrial dyes, schistomiasis, radiation exposure, and certain geographical locations. Well‐defined molecular prognosticators have been identified and, in combination with improved staging techniques, have led to improved outcomes. Patients with nonmuscle invasive urothelial malignancy are best managed by surgical resection, often in combination with intravesical immunotherapy or chemotherapy. Muscle invasive disease is best managed by neoadjuvant cisplatin‐based chemotherapy followed by cystectomy; less robust patients are often effectively treated by cisplatin‐based chemoradiation. Patients with metastatic disease achieve response rates of up to 70% with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or GC combination chemotherapy but are infrequently cured. New approaches to the management of systemic disease are predicated on recent data reflecting the importance of unblocking checkpoints for immune function and correlate with expression of PD‐L1 (programmed death‐ligand 1).
Soft Tissue Sarcomas
Authors: Maki Robert G. , Raut Chandrajit P. , O'Sullivan Brian
Published: August 2023

Overview

The management of soft tissue sarcomas is driven by the anatomic site and histology of the primary and is increasingly affected by the specific genetics of the sarcoma. In this chapter, we focus on the principles of management of this group of over 50 cancer subtypes to highlight commonalities and differences from anatomical constraints of surgery to specifics of adjuvant radiation to identification of systemic therapeutics that are appropriate for each histology.

We will discuss in this chapter the etiology, presentation, diagnosis, staging, and multidisciplinary management of patients with sarcomas of soft tissue. Surgery remains paramount to achieve cure for the vast majority of sarcomas. Radiation therapy is used for larger tumors in the appropriate clinical context. The evolution of increasingly sophisticated radiation techniques is highlighted in this chapter. As pertains to systemic therapy, this chapter is written at a time in which first‐line therapies for soft tissue sarcomas may change, raising anew some questions of adjuvant therapy that remain incompletely answered. Where appropriate, we attempt to link specific histologies or molecular changes to therapeutic suggestions, with the understanding and hope that novel agents will supplant the medications that are available but that have not materially affected outcomes for few diagnoses other than GIST in the past several years.
Myeloproliferative Neoplasms: Essential Thrombocythemia, Primary Myelofibrosis, and Polycythemia Vera
Authors: Tefferi Ayalew
Published: August 2023

Overview

The chronic myeloid neoplasms are a diverse group of malignant bone marrow conditions that originate in a transformed multipotential hematopoietic progenitor cell. This heterogeneous group of diseases shares an initially indolent clinical course with a variable degree of risk to evolve into overt acute leukemia. Even in the absence of leukemic transformation, the consequences of the cellular excesses or deficiencies characteristic of these disorders are troublesome for patients and all too frequently fatal; some of these disease complications include thrombosis, bleeding, marked hepatosplenomegaly, profound constitutional symptoms, and cachexia.
Neoplasms of Unknown Primary Site
Authors: Hainsworth John D. , Greco F. Anthony
Published: August 2023

Overview

Cancer of unknown primary site (CUP) is a clinical syndrome accounting for 2–3% of all cancer diagnoses. This heterogeneous group is comprised of patients who have no anatomic primary site identified after a standard clinical evaluation. Complete pathologic evaluation is essential. Accurate prediction of the tissue of origin, based on examination of a biopsy from a metastatic lesion, is now possible in most patients using improved immunoperoxidase stains and molecular gene expression profiling. After completion of clinical and pathologic diagnostic evaluation, approximately 20% of patients with carcinoma of unknown primary site are included in favorable prognosis subsets and require specific treatment as detailed in this chapter. Until recently, the remaining 80% of patients have been treated with empiric combination chemotherapy. However, as therapy for various solid tumors improves and becomes more site specific, empiric chemotherapy is less likely to provide optimal treatment. Site‐specific therapy directed by the tissue of origin predicted by molecular profiling or immunoperoxidase staining is now appropriate for these patients. New data supporting the use of site‐specific therapy are reviewed.
Anorexia and Cachexia
Authors: Ohnuma Takao
Published: August 2023

Overview

Cancer cachexia is a wasting syndrome with extensive loss of skeletal muscle mass with or without adipose tissue. It may be contrasted with simple starvation in which fat replaces glucose as the preferred fuel to spare lean body mass. It results from altered metabolism rather than just an energy deficit, and cannot be reversed by conventional nutritional support. The causes of cancer‐related cachexia are multifactorial including production of procachectic cytokines and metabolic derangements. European cancer community is credited in developing new definition and classification of cancer cachexia. Recent studies identified anamorelin, an oral ghrelin analogue, as a new agent for the treatment of cancer cachexia.
Neurologic Complications of Cancer
Authors: DeAngelis Lisa M.
Published: August 2023

Overview

Neurologic complications of cancer are common and being seen with increased frequency as patients survive longer with better systemic disease control. Metastases can involve the brain, dura, subarachnoid space, spinal cord, roots, and nerve plexus. Chemotherapy can cause acute toxicities, such as encephalopathy from ifosfamide, which impede the delivery of a full course of effective anticancer treatment. In addition, the long‐term complications of radiotherapy such as radiation myelopathy, and chemotherapy such as peripheral neuropathy, can markedly impair quality of life. Early identification, treatment, and prevention strategies can reduce these toxicities in our growing population of survivors.
Dermatologic Complications of Cancer Chemotherapy
Authors: Patel Anisha B. , Duvic Madeleine M.
Published: August 2023

Overview

Dermatologic complications of cancer chemotherapy have become increasingly significant, especially with the continued development of new targeted antineoplastic agents. The frequency of mucocutaneous complications in cancer chemotherapy is often a reflection of the increased proliferative nature of affected tissues, such as the mucous membranes, skin, hair, and nails, which renders them particularly susceptible to the actions of chemotherapeutic drugs. This chapter reviews the specific side effects associated with targeted therapies and the more classic side effects of cytotoxic chemotherapies and their associated drugs.
Gonadal Complications
Authors: Narayanan Vignesh , Klein Catherine E.
Published: August 2023

Overview

Improvements in cancer therapy over the past 50 years have allowed survivors of pediatric sarcomas and leukemias, and young adults with high‐grade lymphomas, Hodgkin disease, and testicular tumors to reach adulthood but suffer the long‐term consequences of those therapies. Alterations in gonadal function are frequent and distressing side effects of modern cancer therapy. Women face symptoms of premature ovarian failure, including menopause, sterility, and presumably accelerated osteoporosis and possible early heart disease. Men experience oligo‐azoospermia and subclinical Leydig cell dysfunction, leading to infertility and long‐term effects of “andropause” including decreased bone density, lean muscle mass, decreased libido, and increased risk of coronary artery disease.

With recognition has come better documentation of the frequency and severity of these complications, more effective patient counseling, and innovative approaches to attenuate gonadal toxicity. Options include hormonal manipulation, selection of alternative treatments, and pretreatment cryopreservation of embryos or germ cells, but these choices must be offered pretherapy, and patients remain uninformed of potential loss of fertility or options to preserve it. As cancer therapies improve and the number of cancer survivors increases, the practicing oncologist must address these issues in a timely and sensitive manner.
Sexual Dysfunction
Authors: Schover Leslie R.
Published: August 2023

Overview

Sexual problems related to cancer are usually caused by physiological damage from treatment, but are exacerbated by psychosocial issues such as poor communication, relationship conflict, or preexisting sexual dysfunction. Sexual dysfunction affects almost two‐thirds of the estimated 14 million cancer survivors in the United States, including over 50% of those treated for pelvic or breast cancers and at least 25% for other sites. Optimal treatment is multidisciplinary, addressing both physical damage and coping skills. If a committed relationship exists, it is best to include the partner in education and intervention.
A Vision for Twenty‐First Century Healthcare
Authors: Hood Leroy , Brogaard Kristin , Price Nathan D.
Published: August 2023

Overview

The convergence of system medicine, big data, and patient‐activated social networks is leading to a medicine that is predictive, preventive, personalized, and participatory (P4). P4 medicine has two central thrusts—optimizing wellness and demystifying disease. To bring P4 medicine into the healthcare system, we initiated a longitudinal pilot study generating individual data clouds for 108 well people. The integration of the individual data clouds identified “actionable possibilities” that allow individuals to optimize wellness or avoid disease. We believe that this approach will transform healthcare by decreasing costs, increasing quality, and promoting innovation in a new healthcare sector—scientific wellness.
Transcranial pulse stimulation in the treatment of mild neurocognitive disorders
Authors: Fong Tommy Kwan Hin , Cheung Teris , Ngan Sze Ting Joanna , Tong Kelvin , Lui Wai Yan Vivian , Chan Wai Chi , Wong Corine Sau Man , Cheng Calvin Pak Wing
Published: August 2023

Objective

There are limited effectiveness and potential side effects of existing pharmacological approach in treating mild neurocognitive disorder (NCD). Transcranial pulse stimulation (TPS) applies repetitive single high‐pressure ultrashort shockwave pulses to stimulate the brain, which has been shown to effectively improve cognition in major NCD. However, the effectiveness of TPS in mild NCD patients remained unknown. This study aims to assess the effectiveness and tolerability of TPS with neuro‐navigation in old‐age adults with mild NCD by both clinical and biochemical assessments.

Methods

An open‐label study recruited older adults with mild NCD to receive neuro‐navigated TPS intervention for two weeks with three sessions per week. Assessments included detailed cognitive assessments, APOE genotype, and brain‐derived neurotrophic factor (BDNF).

Results

Nineteen participants (12 females and 7 males) completed the whole TPS interventions with no serious adverse effects reported. Repeated measures ANOVA showed statistically significant effects of time on HK‐MoCA (F (3, 54) = 4.99, P = 0.004), 30‐sec interval of Verbal Fluency Test (F (3, 54) = 2.94, P = 0.041), Stroop interference (F (3, 54) = 3.46, P = 0.023), and Chinese IADL (F (3, 54) = 2.78, P = 0.050) after receiving the intervention. Bonferroni post hoc comparisons on HK‐MoCA showed a significant improvement after intervention. There was no significant change in serum BDNF level.

Interpretation

TPS has brought significant improvement in cognition of elderly with mild NCD. It has a great potential to delay the deterioration of cognition in older adults. The long‐term effect of TPS in cognition would benefit from further large‐scale, randomized, sham‐controlled trials.
Combining Clinical and Biological Data to Predict Progressive Pulmonary Fibrosis in Patients With Systemic Sclerosis Despite Immunomodulatory Therapy
Authors: Volkmann Elizabeth R. , Wilhalme Holly , Assassi Shervin , Kim Grace Hyun J. , Goldin Jonathan , Kuwana Masataka , Tashkin Donald P. , Roth Michael D.
Published: August 2023

Objective

Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc‐related interstitial lung disease (SSc‐ILD).

Methods

Patients with SSc‐ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

Results

Among 112 participants with follow‐up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C‐index of 0.72 (95% confidence interval 0.60‐0.84).

Conclusion

The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc‐ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc‐ILD cohorts to confirm its predictive power.
Role of Telomeres and Telomerase in Parkinson's Disease—A New Theranostics?
Authors: Vellingiri Balachandar , Balasubramani Kiruthika , Iyer Mahalaxmi , Raj Neethu , Elangovan Ajay , Song Kwonwoo , Yeo Han‐Cheol , Jayakumar Namitha , Kinoshita Masako , Thangarasu Ravimanickam , Narayanasamy Arul , Dayem Ahmed Abdal , Prajapati Vijay Kumar , Gopalakrishnan Abilash Valsala , Cho Ssang‐Goo
Published: August 2023

Parkinson's disease (PD) is a complex condition that is significantly influenced by oxidative stress and inflammation. It is also suggested that telomere shortening (TS) is regulated by oxidative stress which leads to various diseases including age‐related neurodegenerative diseases like PD. Thus, it is anticipated that PD would result in TS of peripheral blood mononuclear cells (PBMCs). Telomeres protect the ends of eukaryotic chromosomes preserving them against fusion and destruction. The TS is a normal process because DNA polymerase is unable to replicate the linear ends of the DNA due to end replication complications and telomerase activity in various cell types counteracts this process. PD is usually observed in the aged population and progresses over time therefore, disparities among telomere length in PBMCs of PD patients are recorded and it is still a question whether it has any useful role. Here, the likelihood of telomere attrition in PD and its implications concerning microglia activation, ageing, oxidative stress, and the significance of telomerase activators are addressed. Also, the possibility of telomeres and telomerase as a diagnostic and therapeutic biomarker in PD is discussed.
A Universal Cyclodextrin‐Based Nanovaccine Platform Delivers Epitope Peptides for Enhanced Antitumor Immunity
Authors: Mao Jiarong , Jin Zhetong , Rui Xue , Li Lu , Hou Chengchen , Leng Xuejiao , Bi Xiaolin , Chen Zhipeng , Chen Yugen , Wang Jingjing
Published: August 2023

Currently, there is still an intense demand for a simple and scalable delivery platform for peptide‐based cancer vaccines. Herein, a cyclodextrin‐based polymer nanovaccine platform (CDNP) is designed for the codelivery of peptides with two immune adjuvants [the Toll‐like receptor (TLR)7/8 agonist R848 and the TLR9 agonist CpG] that is broadly applicable to epitope peptides with diverse sequences. Specifically, the cyclodextrin‐based polymers are covalently linked to epitope peptides via a bioreactive bond‐containing cross‐linker (PNC‐DTDE‐PNC) and then physically load with R848 and CpG to obtain CDNP. The CDNP efficiently accumulats in the lymph nodes (LNs), greatly facilitating antigen capture and cross‐presentation by antigen‐presenting cells. The immunogenicity of the epitope peptides is significantly enhanced by the codelivery and synergy of the adjuvants, and the CDNP shows the ability to inhibit tumor progression in diverse tumor‐bearing mouse models. It is concluded that CDNP holds promise as an optimized peptide‐based cancer vaccine platform.
Arteriosclerosis Assessment Based on Single‐Point Fingertip Pulse Monitoring Using a Wearable Iontronic Sensor
Authors: Huang Yi , Zhao Lingyu , Cai Minkun , Zhu Jiaqi , Wang Liu , Chen Xinxing , Zeng Yumin , Zhang Liqing , Shi Jidong , Guo Chuan Fei
Published: August 2023

Arteriosclerosis, which appears as a hardened and narrowed artery with plaque buildup, is the primary cause of various cardiovascular diseases such as stroke. Arteriosclerosis is often evaluated by clinically measuring the pulse wave velocity (PWV) using a two‐point approach that requires bulky medical equipment and a skilled operator. Although wearable photoplethysmographic sensors for PWV monitoring are developed in recent years, likewise, this technique is often based on two‐point measurement, and the signal can easily be interfered with by natural light. Herein, a single‐point strategy is reported based on stable fingertip pulse monitoring using a flexible iontronic pressure sensor for heart‐fingertip PWV (hfPWV) measurement. The iontronic sensor exhibits a high pressure‐resolution on the order of 0.1 Pa over a wide linearity range, allowing the capture of characteristic peaks of fingertip pulse waves. The forward and reflected waves of the pulse are extracted and the time difference between the two waves is computed for hfPWV measurement using Hiroshi's method. Furthermore, a hfPWV‐based model is established for arteriosclerosis evaluation with an accuracy comparable to that of existing clinical criteria, and the validity of the model is verified clinically. The work provides a reliable technique that can be used in wearable arteriosclerosis assessment systems.
Regulating Exciton De‐Trapping of Te4+‐Doped Zero‐Dimensional Scandium‐Halide Perovskite for Fluorescence Thermometry with Record High Time‐Resolved Thermal Sensitivity
Authors: Li Gaoqiang , Chen Xu , Wang Meng , Cheng Shanshan , Yang Dongwen , Wu Di , Han Yanbing , Jia Mochen , Li Xinjian , Zhang Yu , Shan Chongxin , Shi Zhifeng
Published: August 2023

Fluorescence thermometry has been propelled to the forefront of scientific attention due to its high spatial resolution and remote non‐invasive detection. However, recent generations of thermometers still suffer from limited thermal sensitivity (Sr) below 10% change per Kelvin. Herein, this work presents an ideal temperature‐responsive fluorescence material through Te4+‐doped 0D Cs2ScCl5·H2O, in which isolated polyhedrons endow highly localized electronic structures, and the strong electron–phonon coupling facilitates the formation of self‐trapped excitons (STEs). With rising temperature, the dramatic asymmetric expansion of the soft lattice induces increased defects, strong exciton–phonon coupling, and low thermal activation energy, which evokes a rapid de‐trapping process of STEs, enabling several orders of magnitude changes in the fluorescence lifetime over a narrow temperature range. After regulating the de‐trapping process with different Te4+ doping, a record‐high Sr (27.36% K−1) of fluorescence lifetime‐based detection is achieved at 325 K. The robust stability against multiple heating/cooling cycles and long‐term measurements enables a low temperature uncertainty of 0.067 K. Further, the developed thermometers are demonstrated for the remote local monitoring of operating temperature on internal electronic components. It is believed that this work constitutes a solid step towards building the next generation of ultrasensitive thermometers based on low‐dimensional metal halides.
Remarkable Thermochromism in the Double Perovskite Cs2NaFeCl6
Authors: Ji Fuxiang , Klarbring Johan , Zhang Bin , Wang Feng , Wang Linqin , Miao Xiaohe , Ning Weihua , Zhang Muyi , Cai Xinyi , Bakhit Babak , Magnuson Martin , Ren Xiaoming , Sun Licheng , Fahlman Mats , Buyanova Irina A. , Chen Weimin M. , Simak Sergei I. , Abrikosov Igor A. , Gao Feng
Published: August 2023

Lead‐free halide double perovskites (HDPs) have emerged as a new generation of thermochromic materials. However, further materials development and mechanistic understanding are required. Here, a highly stable HDP Cs2NaFeCl6 single crystal is synthesized, and its remarkable and fully reversible thermochromism with a wide color variation from light‐yellow to black over a temperature range of 10 to 423 K is investigated. First‐principles, density functional theory (DFT)‐based calculations indicate that the thermochromism in Cs2NaFeCl6 is an effect of electron–phonon coupling. The temperature sensitivity of the bandgap in Cs2NaFeCl6 is up to 2.52 meVK−1 based on the Varshni equation, which is significantly higher than that of lead halide perovskites and many conventional group‐IV, III–V semiconductors. Meanwhile, this material shows excellent environmental, thermal, and thermochromic cycle stability. This work provides valuable insights into HDPs' thermochromism and sheds new light on developing efficient thermochromic materials.
Anomalous Temperature and Polarization Dependences of Photoluminescence of Metal‐Organic Chemical Vapor Deposition‐Grown GeSe2
Authors: Lee Eunji , Dhakal Krishna Prasad , Song Hwayoung , Choi Heenang , Chung Taek‐Mo , Oh Saeyoung , Jeong Hu Young , Marmolejo‐Tejada Juan M. , Mosquera Martín A. , Duong Dinh Loc , Kang Kibum , Kim Jeongyong
Published: August 2023

Germanium diselenide (GeSe2) is a 2D semiconductor with air stability, a wide bandgap, and anisotropic optical properties. The absorption and photoluminescence (PL) of single‐crystalline 2D GeSe2 grown by metal‐organic chemical vapor deposition and their dependence on temperature and polarization are studied. The PL spectra exhibit peaks at 2.5 eV (peak A) and 1.8 eV (peak B); peak A displays a strongly polarized emission along the short axis of the crystal, and peak B displays a weak polarization perpendicular to that of peak A. With increasing temperature, peak B shows anomalous behaviors, i.e., an increasing PL energy and intensity. The excitation energy‐dependent PL, time‐resolved PL, and density functional theory calculations suggest that peak A corresponds to the band‐edge transition, whereas peak B originates from the inter‐band mid‐gap states caused by selenium vacancies passivated by oxygen atoms. The comprehensive study on the PL of single‐crystalline GeSe2 sheds light on the origins of light emission in terms of the band structure of anisotropic GeSe2, making it beneficial for the corresponding optoelectronic applications.