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Simple Summary: Colorectal cancer (CRC) stands as the third most common cancer globally and the second leading cause of cancer-related deaths, imposing a substantial health burden. Recent studies highlight a concerning rise in CRC rates among individuals below 50 years old, prompting the American Cancer Society (ACS) to recommend screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference stresses the urgent need for updated screening strategies to tackle suboptimal adherence rates and effectively manage the increasing burden of CRC. Lowering the adenoma detection screening age could aid in early identification of adenomas in asymptomatic younger patients, potentially reshaping disease epidemiology. Current screening options encompass stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. Moreover, blood-based tests are emerging as promising tools for early CRC detection, utilizing innovative techniques and AI algorithms. Medicare mandates specific criteria for national coverage of blood-based tests. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. Despite breakthroughs, accessibility and affordability challenges persist. Adapting healthcare systems to accommodate changing CRC epidemiology is imperative. Lowering the screening age and integrating blood-based tests hold the potential to alleviate the CRC-related burden amidst evolving epidemiology. Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer presents significant challenges due to its high incidence and prevalence, as it is the most common non-skin cancer in men. The timely detection of prostate cancer and its metastasis is crucial for patient outcomes. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its early detection, due to its specificity and membrane localization on tumor cells. Utilizing PSMA-targeting particles in conjunction with positron emission tomography (PET) scans enhances the accuracy of tumor detection compared to PET alone. This advancement has led to innovative treatment modalities such as Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRTs), which have shown promise in reducing or eliminating tumors, as evidenced by declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both benefits and adverse effects, with the long-term ones as yet unknown. The short-term adverse effects include fatigue, nausea, pain flares, and potential radiation exposure to others. Further research is needed to explore PSMA-TRT's long-term efficacy and potential applications beyond prostate cancer. Prostate cancer is one of the most challenging malignancies due to its high incidence and prevalence, as it is the most frequently diagnosed non-skin cancer in men. The timely identification of prostate cancer and its metastasis is paramount for ensuring favorable outcomes for patients. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its detection, due to its specificity. This makes it an ideal target for the early identification of a metastatic phenotype. Situated on the membrane of tumor cells, PSMA facilitates the attachment of PSMA-targeting particles, enabling their detection through positron emission tomography (PET) scans with relative ease. Utilizing these imaging agents in conjunction with PET scans enhances the accuracy of prostate cancer tumor detection compared to PET scans alone. The advancement in prostate cancer imaging has paved the way for innovative treatment modalities. Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRT) exploit PSMA imaging agents to target identified prostate cancer malignancies with precise radiation, thereby reducing or eliminating the tumor mass. PSMA-TRT exhibits significant promise in prostate cancer therapy, evident from the notable declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both beneficial and adverse effects. While it represents a substantial leap forward in tumor cell imaging, PSMA-based antigens, being larger particles than ligands, offer prolonged imaging capabilities. Yet, the long-term effects of PSMA-TRT remain unknown, with the short-term adverse ones including fatigue, nausea, pain flares, and potential radiation exposure to others. [ABSTRACT FROM AUTHOR]

Simple Summary: This review begins by exploring the escalating global population of cancer survivors, drawing inspiration from Dr. Lidia Schapira's Keynote Conference on Survivorship 1.0 and Survivorship 2.0 Programs. It presents and discusses the transformed and constantly evolving landscape of cancer care, emphasizing patient-centric strategies within Cancer Survivorship Programs, including connection, support, and education. While spotlighting cancer recurrence surveillance, concerns arise regarding potential oversights in addressing the enduring mental and physical health impacts. The study further navigates mental health challenges faced by survivors providing strategies to mitigate them, insights into promising research areas, such as Precision Medicine's role in de-escalating oncology therapies, as well as advocating for early cancer awareness and referrals to supportive services. Dr. Schapira's insights also extend to examining online resources, emphasizing their role in educating healthcare practitioners and future generations in cancer care. Additionally, the paper aims to identify knowledge gaps in cancer care and envision future developments toward accurate, holistic care, improving survivor quality of life, and enhancing mental and physical well-being. The constantly escalating population of cancer survivors worldwide has prompted a focused exploration of their unique needs and experiences within the context of healthcare medicine. This review initiates its analysis inspired by Dr. Lidia Schapira's insightful keynote conference on the Survivorship 1.0 and Survivorship 2.0 Programs, shedding light on their implementation challenges and setting the stage for a comprehensive analysis of cancer survivorship initiatives. Within the transformed landscape of cancer care, patient-centric strategies embedded in cancer survivorship programs comprising vital elements such as connection, support, and education are presented. While placing cancer recurrence surveillance at the forefront, the review underlines concern regarding the potential oversight of the enduring impact on mental and physical health. Dr. Schapira's insights further extend into the exploration of mental health challenges faced by survivors, promoting an examination of diverse strategies to address these concerns. Furthermore, the discussion continues toward promising areas of research, notably Precision Medicine's role in de-escalating cancer therapies, and advocates for measures such as early cancer awareness and timely referrals to supportive services. Highlighting the significance of education, the role of online resources in enhancing the knowledge of healthcare practitioners and future generations in cancer care is then explored. The paper concludes by presenting some of the most prominent global current survivorship programs, identifying critical knowledge gaps in cancer care and projecting future developments aimed at delivering accurate and holistic care, improving the quality of life for survivors, and enhancing both mental and physical well-being. Drawing upon the insights from Dr. Schapira, this review lays the groundwork for a nuanced exploration of cancer survivorship and its multifaceted implications. [ABSTRACT FROM AUTHOR]

Simple Summary: This article examines the significance of liquid biopsies in the field of thoracic oncology, particularly regarding the diagnosis and treatment of malignancies. These blood-based biopsies, which utilize circulating tumor DNA (ctDNA), are presented as a less invasive method for both the diagnosis and monitoring of cancer cells and offer a dynamic means of tracking tumors, allowing for personalized treatment approaches and real-time information about the tumor's status throughout its natural history. The analysis of biomarkers through blood samples could therefore lessen the need for more invasive tissue biopsies. The article also addresses the valuable role circulating biomarker analyses play in allowing treatment plans to be modified according to the genetic changes observed in the tumor. The importance of adapting to genetic aberrations that may develop during treatment is highlighted, emphasizing the need for timely adjustments to ensure a therapy's effectiveness. In summary, the article underscores the potential of liquid biopsies to revolutionize thoracic cancer care by offering a minimally invasive and personalized approach to diagnosis and treatment, emphasizing the importance of their further advancement. Thoracic oncology continues to pose a great threat to human health as one of the most common forms of cancer. Liquid biopsies present a transformative approach to treating patients affected by these types of diseases by providing a less invasive genetic overview of the tumor, aiding in both diagnostic and treatment measures. The primary objective of this article is to examine the prospects of liquid biopsies in managing thoracic malignancies and to present barriers to their usage as demonstrated by Dr. Luis Raez. In examining why molecular diagnostics continue to be employed together with more traditional methods, this article presents the next steps in the clinical application of blood-based cancer screening. Future cancer diagnosis and treatment aim to prioritize circulating biomarker analyses based on their potential for the detection and monitoring of thoracic cancers. Liquid biopsies are favored thanks to their reduced invasiveness with respect to traditional treatments. The further study of clinical biomarkers and technological advancements are thus pivotal to enhance the clinical applicability of this method. In conclusion, this blood-based analysis offers a promising route by which the diagnosis, treatments, and outcomes of thoracic cancer can be improved. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract malignancies, including cholangiocarcinoma (CCA) and gallbladder neoplasms, present intricate challenges in diagnosis and treatment. This comprehensive overview highlights the diversity of CCA subtypes, their genetic underpinnings, and the pivotal role of etiological factors. Despite diagnostic complexities, advancements in genomic sequencing reveal promising therapeutic targets, such as FGFR2 alterations and IDH1 mutations. Dr. James Cleary's insights underscore the potential of these targets in reshaping the treatment landscape. This paper provides insights into the conventional understanding of biliary tract malignancies and emphasizes the critical need for ongoing research to optimize outcomes in this challenging cancer subtype. By elucidating diverse FGFR2 alterations and the potential of IDH1 inhibition, the aim is to pave the way for targeted therapeutic interventions. As we delve deeper into understanding the intricate complexities of biliary tract malignancies, this research seeks to drive precision medicine forward, offering hope for improved treatment strategies and outcomes in the face of this formidable cancer. This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary. [ABSTRACT FROM AUTHOR]

Simple Summary: This collection of discussions by an experienced speaker explores the evolving landscape of lifestyle medicine in the context of cancer care and survivorship. Emphasizing the critical role of lifestyle modifications, the discussions address challenges and opportunities in optimizing cancer survivors' health and mitigating late effects in pediatric populations. The importance of education, patient-centered communication, and access to resources is underscored, as well as the healthcare professional's ability to effectively support lifestyle changes. The collection also reflects on the role of nutritionists in guiding breast cancer patients considering calorie restriction. Ultimately, these insights illuminate the multifaceted nature of lifestyle medicine in cancer care and highlight the transformative power of passion and curiosity in healthcare careers. The field of lifestyle medicine in cancer care and survivorship is undergoing significant transformation, presenting both challenges and opportunities. This collection of insights and reflections by an esteemed speaker aims to address critical facets of this evolving landscape and the intersection of healthcare, lifestyle, and cancer. With a focus on optimizing the health of cancer survivors, the speaker emphasizes the correlation between general population health and strategies for mitigating cancer risk. Evidence-based resources have a key role in their comprehensive insights into lifestyle changes' role in cancer prevention and survivorship. Lifestyle interventions also have a promising role in mitigating the late effects in the pediatric context. Therefore, encouraging the early adoption of healthy practices in childhood cancer survivors emerges as a pivotal strategy. Furthermore, challenges in enhancing education and access to lifestyle medicine are addressed. This highlights the importance of patient-centered communication, motivational interviewing, and personalized guidance in facilitating lifestyle changes with patients. Finally, the role of nutritionists in advising breast cancer patients to consider calorie restriction to lower IGF-1 levels is explored. This collection underscores the multifaceted nature of lifestyle medicine in cancer care, highlighting challenges, opportunities, and the transformative power of passion and curiosity in shaping healthcare careers. [ABSTRACT FROM AUTHOR]

Simple Summary: Current research is exploring the evolving landscape of Myelodysplastic Syndrome (MDS) treatment, a challenging condition often progressing to acute myeloid leukemia. For low-risk MDS, the focus is on personalized care through precise risk assessment and tailored interventions, utilizing means like erythropoiesis-stimulating agents, lenalidomide, and luspatercept. High-risk MDS treatments are shifting towards upfront doublet or triplet therapies and minimal residual disease (MRD) monitoring. A holistic approach integrates treatments like stem cell transplants and post-transplant maintenance, guided by individual patient circumstances. Precision medicine, driven by Next Generation Sequencing (NGS), aids in early diagnosis, prognosis, and customized interventions, allowing for investigations through clinical trials within more homogeneous patient cohorts characterized by similar molecular profiles. Based on these premises, the future of MDS treatment irrefutably moves towards personalized care, leveraging advanced technologies and molecular insights to enhance patient outcomes in the realm of hematological malignancies. This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through comprehensive risk assessment, clinical monitoring, and tailored interventions, including promising agents like erythropoiesis-stimulating agents, lenalidomide, and luspatercept, with the anticipation of an expanding therapeutic arsenal and early intervention for improved outcomes. In contrast, high-risk MDS treatment is evolving towards upfront doublet or triplet therapies with a focus on minimal residual disease (MRD) monitoring. A holistic approach integrates various modalities, including stem cell transplant and post-transplant maintenance, all guided by individual patient circumstances. Risk-adapted strategies are crucial for enhancing patient outcomes. Precision medicine for MDS treatment is budding, largely driven by Next Generation Sequencing (NGS). NGS aids in early diagnosis, prognostication, and the targeting of specific mutations, with molecular data increasingly informing treatment responses and allowing for tailored interventions. Clinical trials within homogeneous patient groups with similar molecular profiles are becoming more common, enhancing treatment precision. In conclusion, the future of MDS treatment is moving towards personalized medicine, leveraging advanced technologies like NGS and molecular insights to improve outcomes in the realm of hematological malignancies. [ABSTRACT FROM AUTHOR]

COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of access to clinical electives and protocol workshops, delays in research approval and execution, mentor shortages due to academic burnout, and obstacles with career transitions (most notably the post-fellowship job search). While certain silver linings from the pandemic have undoubtedly emerged, continued progress against COVID-19 will be essential to fully overcome the professional challenges it has created for the future hematology/oncology workforce. [ABSTRACT FROM AUTHOR]

The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals. [ABSTRACT FROM AUTHOR]

Large randomized controlled trials (RCTs) remain the gold standard for evaluating treatment efficacy. However, observational studies, including non-randomized cohort studies, as well as small RCTs have gained increasing attention especially during the SARS-CoV-2 pandemic where critical evaluation of limited therapeutic options are sought to improve patient care while awaiting results for subsequent RCTs. As the authors have previously discussed, RCTs and observational studies are complementary approaches which often appear synergistic with one another. While not all real-world studies are the same, the results of observational studies are notoriously subject to both known and unknown confounding factors. The utilization of COVID-19 Convalescent Plasma is a timely illustration of evaluating the efficacy and safety of a COVID-19 therapy given the dangerous and often lethal effects of the virus and the limited approved therapeutic options for the disease. While awaiting the results of large RCTS of convalescent plasma, serval observational cohorts and small RCTs have attempted to assess the efficacy and safety of this approach with very mixed results. Among the likely reasons for this failure to provide a definitive answer concerning the value of convalescent plasma are the many limitations inherent to addressing treatment efficacy in non-randomized studies. While such studies are often able to capture information on large numbers of individuals rapidly, it is important to understand that although larger numbers may enhance the precision of estimates provided, larger numbers, in and of themselves, do not increase the accuracy of estimates due to patient selection and other biases. At the same time, both observational studies and small RCTS are at risk for publication bias due to investigator, reviewer and editorial bias toward positive studies. In this commentary we discuss the advantages and limitations of these methodologic approaches when addressing urgently needed evidence on the effectiveness and safety of therapies in a crisis such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Abstract Background Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs) responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a) to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b) to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214. Results Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SABiosciences) revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 μM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and FACS data were confirmed with western blotting. Importantly, viable cells that survived this treatment regimen were no longer able to induce secondary floating spheroids and exhibited significant morphological abnormalities. Conclusions We report here that a new-generation taxoid SB-T-1214 possesses significant activity against colon cancer spheroids induced by and enriched with drug resistant tumorigenic CD133high/CD44high cells and efficiently inhibited expression of the majority of stem cell-related genes. Our data indicates that the previously observed long-term efficacy of SB-T-1214 against drug resistant colon tumors in vivo may be explained by the down-regulation of multiple stem cell-related genes in the tumorigenic cell population, in addition to its known efficacy as a mitotic poison against proliferating cancer cells.

Background: Chimeric antigen receptors (CARs) represent a novel facet of modern day synthetic biology that exemplifies personalized medicine at work through their ability to harness and redirect a patient's immune system to fight cancer. Body: By combining the target-specificity of antibodies to the effector capabilities of T cells, CARs have yielded high remission rates for many late staged and relapsed/refractory (r/r) hematological malignancies, including acute lymphoblastic leukemias (ALL) and Non-Hodgkin's lymphomas. Despite toxicities of cytokine release syndrome and neurotoxicity, recent studies have uncovered their underlying mechanisms and devised effective therapies to manage and possibly prevent them. In 2017, CAR T cell therapy became a reality for the general public despite the high costs, when Novartis's Kymriah, became the first product to receive FDA approval for pediatric r/r B cell ALL with Gilead's Yescarta following several months later. Although effective in hematological malignancies, CAR response has been limited in solid tumors largely attributed to the heterogeneous and immunosuppressive tumor microenvironment along tumor defense mechanisms, such as antigenic escape. Conclusion: Despite the current challenges of CAR T therapy, this technology is still in its infancy and its promise will continue to grow as scientists continue to develop novel approaches to enhance its efficacy. As its prevalence continues to increase, institutions and pharmaceuticals worldwide are investing in this technology in hopes of driving therapeutic innovation, while providing greater access to their respective populations through clinical trials. [ABSTRACT FROM AUTHOR]

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus , was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a "new normal" are discussed in this article., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Global Infectious Diseases.)

Background: Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs) responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a) to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b) to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214., Results: Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SABiosciences) revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 microM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and FACS data were confirmed with western blotting. Importantly, viable cells that survived this treatment regimen were no longer able to induce secondary floating spheroids and exhibited significant morphological abnormalities., Conclusions: We report here that a new-generation taxoid SB-T-1214 possesses significant activity against colon cancer spheroids induced by and enriched with drug resistant tumorigenic CD133high/CD44high cells and efficiently inhibited expression of the majority of stem cell-related genes. Our data indicates that the previously observed long-term efficacy of SB-T-1214 against drug resistant colon tumors in vivo may be explained by the down-regulation of multiple stem cell-related genes in the tumorigenic cell population, in addition to its known efficacy as a mitotic poison against proliferating cancer cells.

Background: Human cancer is characterized by high heterogeneity in gene expression, varieties of differentiation phenotypes and tumor-host interrelations. Growing evidence suggests that tumor-initiating, or cancer stem cells (CSCs), may also represent a heterogeneous population. The present study was undertaken to isolate and characterize the different phenotypic subpopulations of metastatic colon cancer and to develop a working colon CSC model for obtaining highly tumorigenic and clonogenic cells in sufficient numbers., Materials and Methods: Different phenotypic cell subpopulations were isolated based on differential levels and patterns of expression of several stemness markers, including CD133, CD44, CD166 and CD49b. Stemness properties of isolated cells were tested by analysis of their ability to form floating colonospheres in vitro, to induce tumors in NOD/SCID mice after transplantation at relatively low cell numbers, and to produce progenitors of different phenotypes., Results: The metastatic colon cancer HCT116 cell line, which expressed a majority of known CSC markers, closely resembling the patterns of expression in exfoliated peritoneal cells from several metastatic colon cancer patients, was selected as a reference material. Genome-wide microarray analysis (Affymetrix; DAVID) of CD133(high) CSC-enriched versus CSC-depleted cell populations revealed 4,351 differentially expressed genes with an overrepresentation of those responsible for apoptosis resistance, regulation of cell cycle, proliferation, stemness and developmental pathways. Simultaneous analysis of 84 stem cell- and metastasis-related genes with corresponding PCR arrays identified genes differentially expressed in several colon CSC phenotypic populations versus bulk tumor cells, and in relation to each other. It was found that colonospheres induced by tumorigenic cells with the highest expression of CD133 and those which were induced by CD133/CD44-negative cells possessed profoundly different stem cell-related gene expression profiles., Conclusion: The proposed approaches allow for reliable isolation and propagation of highly tumorigenic and clonogenic cells of different phenotypes. Genomic analysis of several candidate CSC phenotypic populations may contribute to the identification of novel targets for colon cancer stem cell-targeted drug development and treatment.