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Seminars in Cancer Biology Oct 2018Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung... (Review)
Review
Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy.
Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung carcinoma (NSCLC). These findings not only lead to remarkable progress in targeted therapies for lung cancer patients, but also provide fundamental knowledge for the subclassification of NSCLC. More recently, the advancement and clinical application of immunotherapy have reinforced the need for the accurate subclassification of NSCLC. In 2015, the World Health Organization (WHO) and the International Association for the Study of Lung Cancer (IASLC) updated their guidelines for the subclassification of lung cancers. These guidelines emphasize: (1) the subclassification of NSCLC, (2) the critical role of molecular characterization of tumors for targeted therapy, (3) the unique terminology for subclassifying NSCLC using small biopsy specimens, and (4) the utility of IHC biomarkers in the accurate diagnosis and subclassification of lung cancer. The guidelines have significant prognostic impact on oncologic practice and patient care. In this review, we summarize the current WHO guidelines for the classification of lung cancer, discuss advancements of targeted therapy and immunotherapy, and address the utility and limitation of immunomarkers in the subclassification of NSCLC, as well as the prospective future of the field.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Immunohistochemistry; Immunotherapy; Lung Neoplasms; Molecular Targeted Therapy; Practice Guidelines as Topic; World Health Organization
PubMed: 29183778
DOI: 10.1016/j.semcancer.2017.11.019 -
Nature Reviews. Cancer Feb 2022Advances in quantitative biomarker development have accelerated new forms of data-driven insights for patients with cancer. However, most approaches are limited to a... (Review)
Review
Advances in quantitative biomarker development have accelerated new forms of data-driven insights for patients with cancer. However, most approaches are limited to a single mode of data, leaving integrated approaches across modalities relatively underdeveloped. Multimodal integration of advanced molecular diagnostics, radiological and histological imaging, and codified clinical data presents opportunities to advance precision oncology beyond genomics and standard molecular techniques. However, most medical datasets are still too sparse to be useful for the training of modern machine learning techniques, and significant challenges remain before this is remedied. Combined efforts of data engineering, computational methods for analysis of heterogeneous data and instantiation of synergistic data models in biomedical research are required for success. In this Perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods. Advancing along this direction will result in a reimagined class of multimodal biomarkers to propel the field of precision oncology in the coming decade.
Topics: Artificial Intelligence; Genomics; Humans; Medical Oncology; Neoplasms; Precision Medicine
PubMed: 34663944
DOI: 10.1038/s41568-021-00408-3 -
Frontiers in Immunology 2018NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit... (Review)
Review
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined. Finally, we describe the immune-based therapeutic options targeting NY-ESO-1 that are currently in clinical trial. We will highlight the recent advancements made in NY-ESO-1 cancer vaccines, adoptive T cell therapy, and combinatorial treatment with checkpoint inhibitors and will discuss the current trends for future NY-ESO-1 based immunotherapy. Cancer treatment has been revolutionized over the last few decades with immunotherapy emerging at the forefront. Immune-based interventions have shown promising results, providing a new treatment avenue for durable clinical responses in various cancer types. The majority of successful immunotherapy studies have been reported in liquid cancers, whereas these approaches have met many challenges in solid cancers. Effective immunotherapy in solid cancers is hampered by the complex, dynamic tumor microenvironment that modulates the extent and phenotype of the antitumor immune response. Furthermore, many solid tumor-associated antigens are not private but can be found in normal somatic tissues, resulting in minor to detrimental off-target toxicities. Therefore, there is an ongoing effort to identify tumor-specific antigens to target using various immune-based modalities. CTAs are considered good candidate targets for immunotherapy as they are characterized by a restricted expression in normal somatic tissues concomitant with a re-expression in solid epithelial cancers. Moreover, several CTAs have been found to induce a spontaneous immune response, NY-ESO-1 being the most immunogenic among the family members. Hence, this review will focus on NY-ESO-1 and discuss the past and current NY-ESO-1 targeted immunotherapeutic strategies.
Topics: Animals; Antigens, Neoplasm; Biomarkers, Tumor; Cancer Vaccines; Clinical Trials as Topic; Combined Modality Therapy; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunity; Immunotherapy; Immunotherapy, Adoptive; Membrane Proteins; Molecular Targeted Therapy; Neoplasms; Organ Specificity; Treatment Outcome
PubMed: 29770138
DOI: 10.3389/fimmu.2018.00947 -
International Journal of Environmental... Mar 2020Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic... (Review)
Review
Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic target due to their highly invasive nature and relatively low response to therapeutics. There is an absence of specific treatment strategies for this tumor subgroup, and hence TNBC is managed with conventional therapeutics, often leading to systemic relapse. In terms of histology and transcription profile these cancers have similarities to BRCA-1-linked breast cancers, and it is hypothesized that BRCA1 pathway is non-functional in this type of breast cancer. In this review article, we discuss the different receptors expressed by TNBC as well as the diversity of different signaling pathways targeted by TNBC therapeutics, for example, Notch, Hedgehog, Wnt/b-Catenin as well as TGF-beta signaling pathways. Additionally, many epidermal growth factor receptor (EGFR), poly (ADP-ribose) polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors effectively inhibit the TNBCs, but they face challenges of either resistance to drugs or relapse. The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed. Artificial intelligence is another tool that is presented to enhance the diagnosis of TNBC.
Topics: Artificial Intelligence; Female; Humans; Neoplasm Recurrence, Local; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Receptors, Cell Surface; Signal Transduction; Triple Negative Breast Neoplasms
PubMed: 32245065
DOI: 10.3390/ijerph17062078 -
World Journal of Gastroenterology Aug 2021Gastric cancer accounts for a significant proportion of worldwide cancer-related morbidity and mortality. The well documented precancerous cascade provides an... (Review)
Review
Gastric cancer accounts for a significant proportion of worldwide cancer-related morbidity and mortality. The well documented precancerous cascade provides an opportunity for clinicians to detect and treat gastric cancers at an endoscopically curable stage. In high prevalence regions such as Japan and Korea, this has led to the implementation of population screening programs. However, guidelines remain ambiguous in lower prevalence regions. In recent years, there have been many advances in the endoscopic diagnosis and treatment of early gastric cancer and precancerous lesions. More advanced endoscopic imaging has led to improved detection and characterization of gastric lesions as well as superior accuracy for delineation of margins prior to resection. In addition, promising early data on artificial intelligence in gastroscopy suggests a future role for this technology in maximizing the yield of advanced endoscopic imaging. Data on endoscopic resection (ER) are particularly robust in Japan and Korea, with high rates of curative ER and markedly reduced procedural morbidity. However, there is a shortage of data in other regions to support the applicability of protocols from these high prevalence countries. Future advances in endoscopic therapeutics will likely lead to further expansion of the current indications for ER, as both technology and proceduralist expertise continue to grow.
Topics: Artificial Intelligence; Dissection; Gastroscopy; Humans; Republic of Korea; Stomach Neoplasms
PubMed: 34497440
DOI: 10.3748/wjg.v27.i31.5126 -
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 -
World Journal of Gastroenterology May 2023Gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Less than half of GC cases are diagnosed at an advanced stage due to its lack of early... (Review)
Review
Gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms. GC is a heterogeneous disease associated with a number of genetic and somatic mutations. Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality. The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers: However, these approaches are invasive, costly, and time-consuming. Thus, novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods. Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease. These biomarkers include circulating DNA, RNA, extracellular vesicles, and proteins, and their clinical applications are currently being investigated. The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine. This review provides an overview of current topics regarding the novel, recently developed diagnostic markers for GC.
Topics: Humans; Stomach Neoplasms; Biomarkers, Tumor; Early Detection of Cancer; Cell-Free Nucleic Acids
PubMed: 37213407
DOI: 10.3748/wjg.v29.i17.2515 -
Journal of Thoracic Oncology : Official... Feb 2022This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors... (Review)
Review
This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1 phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.
Topics: Adenocarcinoma; Germ Cells; Humans; Lung Neoplasms; Mediastinum; Thymus Neoplasms; World Health Organization
PubMed: 34695605
DOI: 10.1016/j.jtho.2021.10.010 -
Frontiers in Immunology 2022Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal.... (Review)
Review
Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal. For patients with resectable disease, neoadjuvant chemoradiotherapy (nCRT) in combination with esophagectomy is the mainstay of treatment. However, the pathological complete response (pCR) rate to nCRT of 29.2% to 43.2% is not satisfactory, and approximately half of the patients will develop either a locoregional recurrence or distant metastasis. It is, therefore, necessary to explore novel and effective treatment strategies to improve the clinical efficacy of treatment. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has significantly changed the treatment paradigm for a wide variety of advanced cancers, including EC. More recently, increasing clinical evidence has demonstrated that neoadjuvant immunotherapy can potentially improve the survival of patients with resectable cancers. Furthermore, accumulating findings support the idea that chemotherapy and/or radiotherapy can activate the immune system through a variety of mechanisms, so a combination of chemotherapy and/or radiotherapy with immunotherapy can have a synergistic antitumor effect. Therefore, it is reasonable to evaluate the role of neoadjuvant immunotherapy for patients with surgically resectable EC. In this review, we discuss the rationale for neoadjuvant immunotherapy in patients with EC, summarize the current results of utilizing this strategy, review the planned and ongoing studies, and highlight the challenges and future research needs.
Topics: Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Esophageal Neoplasms; Treatment Outcome; Immunotherapy
PubMed: 36569908
DOI: 10.3389/fimmu.2022.1051841