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Cancer Cell Sep 2023Among new treatment approaches for patients with cancer, few have accelerated as quickly as neoadjuvant immune checkpoint blockade (ICB). Neoadjuvant cancer therapy is... (Review)
Review
Among new treatment approaches for patients with cancer, few have accelerated as quickly as neoadjuvant immune checkpoint blockade (ICB). Neoadjuvant cancer therapy is administered before curative-intent surgery in treatment-naïve patients. Conventional neoadjuvant chemotherapy and radiotherapy are primarily intended to reduce tumor size, improving surgical resectability. However, recent scientific evidence outlined here suggests that neoadjuvant immunotherapy can expand and transcriptionally modify tumor-specific T cell clones to enhance both intratumoral and systemic anti-tumor immunity. It further offers a unique "window of opportunity" to explore mechanisms and identify novel biomarkers of ICB response and resistance, opening possibilities for refining long-term clinical outcome predictions and developing new, more highly effective ICB combination therapies. Here, we examine advances in clinical and scientific knowledge gleaned from studies in select cancers and describe emerging key principles relevant to neoadjuvant ICB across many cancer types.
Topics: Humans; Neoadjuvant Therapy; Immune Checkpoint Inhibitors; Immunotherapy; Clone Cells; Neoplasms
PubMed: 37595586
DOI: 10.1016/j.ccell.2023.07.011 -
Cancer Cell Feb 2024The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, the newly developed treatment... (Review)
Review
The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, the newly developed treatment strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision treatment represents a paradigm shift in cancer treatment in recent years. This approach utilizes the unique molecular characteristics of individual patient to personalize treatment modalities, aiming to maximize therapeutic efficacy while minimizing side effects. Although precision treatment has shown significant success in multiple cancer types, its application in HCC remains in its infancy. In this review, we discuss key aspects of precision treatment in HCC, including therapeutic biomarkers, molecular classifications, and the heterogeneity of the tumor microenvironment. We also propose future directions, ranging from revolutionizing current treatment methodologies to personalizing therapy through functional assays, which will accelerate the next phase of advancements in this area.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 38350421
DOI: 10.1016/j.ccell.2024.01.007 -
Medicine Jan 2024Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the... (Review)
Review
Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the multifaceted landscape of breast cancer, elucidating the diverse spectrum of risk factors contributing to its occurrence and exploring advancements in diagnostic methodologies. Through an extensive examination of current literature, various risk factors have been identified, encompassing genetic predispositions such as BRCA mutations, hormonal influences, lifestyle factors, and reproductive patterns. Age, family history, and environmental factors further contribute to the intricate tapestry of breast cancer etiology. Moreover, this review delineates the pivotal role of diagnostic tools in the early detection and management of breast cancer. Mammography, the cornerstone of breast cancer screening, is augmented by emerging technologies like magnetic resonance imaging and molecular testing, enabling improved sensitivity and specificity in diagnosing breast malignancies. Despite these advancements, challenges persist in ensuring widespread accessibility to screening programs, particularly in resource-limited settings. In conclusion, this review underscores the importance of understanding diverse risk factors in the development of breast cancer and emphasizes the critical role of evolving diagnostic modalities in enhancing early detection. The synthesis of current knowledge in this review aims to contribute to a deeper comprehension of breast cancer's multifactorial nature and inform future directions in research, screening strategies, and preventive interventions.
Topics: Humans; Female; Breast Neoplasms; Early Detection of Cancer; Mammography; Breast; Risk Factors
PubMed: 38241592
DOI: 10.1097/MD.0000000000036905 -
Cell Mar 2024The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of... (Review)
Review
The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, and the ability to profile circulating tumor fractions. Integrating these insights promises to continually advance the precision oncology field, fostering better patient outcomes.
Topics: Humans; Biomarkers, Tumor; Medical Oncology; Neoplasms; Precision Medicine; Tumor Microenvironment
PubMed: 38552610
DOI: 10.1016/j.cell.2024.02.041 -
Cancer Cell Dec 2023Esophageal squamous cell carcinoma (ESCC) develops through a series of increasingly abnormal precancerous lesions. Previous studies have revealed the striking...
Esophageal squamous cell carcinoma (ESCC) develops through a series of increasingly abnormal precancerous lesions. Previous studies have revealed the striking differences between normal esophageal epithelium and ESCC in copy number alterations (CNAs) and mutations in genes driving clonal expansion. However, due to limited data on early precancerous lesions, the timing of these transitions and which among them are prerequisites for malignant transformation remained unclear. Here, we analyze 1,275 micro-biopsies from normal esophagus, early and late precancerous lesions, and esophageal cancers to decipher the genomic alterations at each stage. We show that the frequency of TP53 biallelic inactivation increases dramatically in early precancerous lesion stage while CNAs and APOBEC mutagenesis substantially increase at late stages. TP53 biallelic loss is the prerequisite for the development of CNAs of genes in cell cycle, DNA repair, and apoptosis pathways, suggesting it might be one of the earliest steps initiating malignant transformation.
Topics: Humans; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma, Squamous Cell; Genomics; Precancerous Conditions
PubMed: 38039962
DOI: 10.1016/j.ccell.2023.11.003 -
Radiology. Imaging Cancer Jul 2023Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired... (Review)
Review
Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.
Topics: United States; Male; Humans; Precision Medicine; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Radioisotopes; Neoplasms
PubMed: 37477566
DOI: 10.1148/rycan.220157 -
Signal Transduction and Targeted Therapy Feb 2024Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and... (Review)
Review
Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery.
Topics: Humans; Extracellular Vesicles; MicroRNAs; Biomarkers; Virus Diseases; Neoplasms; Tumor Microenvironment
PubMed: 38311623
DOI: 10.1038/s41392-024-01735-1 -
The Medical Clinics of North America Nov 2023Although cancer has been the second leading cause of death for close to 100 years, progress has been made in reducing cancer mortality and morbidity, with the adoption... (Review)
Review
Although cancer has been the second leading cause of death for close to 100 years, progress has been made in reducing cancer mortality and morbidity, with the adoption of high-quality screening tests and treatment advances delivered at earlier stages of diagnosis. To achieve the high cancer screening rates demonstrated by some practices, proven effective strategies need to be broadly adopted at both the patient and population levels. Factors affecting cancer screening test completion and approaches to improvement are described both generally and for breast, lung, cervical, colorectal, and prostate cancers. Closing the racial disparity gap is a critical component of reaching cancer screening and prevention goals.
Topics: Male; Humans; Early Detection of Cancer; Prostatic Neoplasms; Mammography; Colorectal Neoplasms; Breast Neoplasms
PubMed: 37806730
DOI: 10.1016/j.mcna.2023.06.002 -
Cell Communication and Signaling : CCS May 2024Cancer's complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in...
Cancer's complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in effective cancer management. Variability within a tumor arises from the existence of diverse populations of cancer cells, impacting the progression, spread, and resistance to treatments. At the core of this variability is the concept of cellular plasticity - the intrinsic ability of cancer cells to alter their molecular and cellular identity in reaction to environmental and genetic changes. This adaptability is a cornerstone of cancer's persistence and progression, making it a formidable target for treatments. Emerging studies have emphasized the critical role of such plasticity in fostering tumor diversity, which in turn influences the course of the disease and the effectiveness of therapeutic strategies. The transformative nature of cancer involves a network of signal transduction pathways, notably those that drive the epithelial-to-mesenchymal transition and metabolic remodeling, shaping the evolutionary path of cancer cells. Despite advancements, our understanding of the precise molecular machinations and signaling networks driving these changes is still evolving, underscoring the necessity for further research. This editorial presents a series entitled "Signaling Cancer Cell Plasticity and Intratumor Heterogeneity" in Cell Communication and Signaling, dedicated to unraveling these complex processes and proposing new avenues for therapeutic intervention.
Topics: Humans; Neoplasms; Cell Plasticity; Signal Transduction; Animals; Epithelial-Mesenchymal Transition
PubMed: 38702718
DOI: 10.1186/s12964-024-01643-5 -
Current Treatment Options in Oncology Dec 2023Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian... (Review)
Review
Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian cancers. It is characterized by high morbidity and mortality rates, with a median overall survival (OS) of less than 2 years. Several factors, including advancing age, nulliparity, reduced lactation rates, decreased use of oral contraceptive pills, genetic mutations in BRCA (breast cancer) genes, and the use of assisted reproductive technology, may increase the risk of OCS. Poor prognostic factors include an advanced stage at diagnosis, older age, lymph node metastasis, suboptimal surgical cytoreduction, the presence of heterologous features on histopathology, and increased expression of vascular endothelial growth factor (VEGF), tumour protein p53, and p53 alongside Wilms tumour 1 (WT1). The main treatment approach for OCS is cytoreductive surgery followed by platinum-based chemotherapy, although immunotherapy is showing promise. Homologous recombination deficiency (HRD) testing may enhance outcomes by enabling personalized immunotherapy and targeted therapies for specific patient groups, thereby reducing unnecessary side effects and healthcare costs. However, there is currently a lack of standardised treatment regimens for OCS patients, with most studies consisting of case reports and a shortage of suitable comparator groups. This article aims to provide clinicians with information on the epidemiology, risk factors, prognostic factors, and latest therapeutic advancements in OCS.
Topics: Female; Humans; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Ovarian Neoplasms; Carcinosarcoma
PubMed: 37938504
DOI: 10.1007/s11864-023-01138-4