scholarly journals Paraneoplastic neurological syndrome: an evolving story

2021 ◽  
Author(s):  
Jiraporn Jitprapaikulsan ◽  
Pritikanta Paul ◽  
Smathorn Thakolwiboon ◽  
Shivam Om Mittal ◽  
Sean J Pittock ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
High Specificity ◽  
Paraneoplastic Neurological Syndrome ◽  
Neurological Syndrome ◽  
Onconeural Antibodies ◽  
Gastrointestinal Dysmotility ◽  
The Past ◽  
Myasthenic Syndrome ◽  
Tumor Types ◽  
Distant Tumor

Abstract Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.

scholarly journals Anti- SOX1 antibody-positive paraneoplastic neurological syndrome presenting with Lambert–Eaton myasthenic syndrome and small cell lung cancer: a case report

2019 ◽  
Author(s):  
Wenqi Zheng ◽  
Xiaolei Wang ◽  
Lihua Sun ◽  
Hui Deng ◽  
Yanqiu Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Symptoms ◽  
Paraneoplastic Neurological Syndrome ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hyperintense Lesion ◽  
Onconeural Antibodies ◽  
Myasthenic Syndrome

Abstract Background Paraneoplastic neurological syndromes (PNS) are rare disorders affecting any part of the central, peripheral or autonomic nervous system that occur in association with cancer. Among cancer patients, less than 1% overall develop PNS. Anti- SOX1 antibodies positive paraneoplastic neurological disorders are rare and most often associated with small cell lung cancer (SCLC). Case presentation Herein, we report a case of a 61-year-old male presented with an unusual anti- SOX1 positive PNS. Electrodiagnostic study showed notable low amplitude motor potentials and high amplitude motor potentials of the right tibialis anterior suggesting the presence of Lambert–Eaton myasthenic syndrome (LEMS). Typical MRI and PET-CT found a hyperintense lesion with contrast enhancement in the thorax in front of 5-6 centrum of vertebrae, and thoracoscopic biopsy revealed pathological findings for SCLC. Because the diagnosis was made in time, the patient is currently receiving chemotherapy and radiotherapy for the cancer at Chinese PLA General Hospital, and the clinical symptoms improved obviously. Conclusions The comprehensive screening of onconeural antibodies in PNS-suspicious cases combined with early diagnosis and treatment of tumor are important for achieving a good outcome.

scholarly journals Telomerase as a Target for Therapeutic Cancer Vaccines and Considerations for Optimizing Their Clinical Potential

2021 ◽  
Vol 12 ◽  
Author(s):  
Espen Basmo Ellingsen ◽  
Sara M. Mangsbo ◽  
Eivind Hovig ◽  
Gustav Gaudernack
Keyword(s):  
Cancer Vaccines ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Clinical Investigation ◽  
Checkpoint Inhibition ◽  
The Past ◽  
Essential Function ◽  
Tumor Types ◽  
Clinical Potential ◽  
Therapeutic Cancer Vaccines

Telomerase-based therapeutic cancer vaccines (TCVs) have been under clinical investigation for the past two decades. Despite past failures, TCVs have gained renewed enthusiasm for their potential to improve the efficacy of checkpoint inhibition. Telomerase stands as an attractive target for TCVs due to its almost universal presence in cancer and its essential function promoting tumor growth. Herein, we review tumor telomerase biology that may affect the efficacy of therapeutic vaccination and provide insights on optimal vaccine design and treatment combinations. Tumor types possessing mechanisms of increased telomerase expression combined with an immune permissive tumor microenvironment are expected to increase the therapeutic potential of telomerase-targeting cancer vaccines. Regardless, rational treatment combinations, such as checkpoint inhibitors, are likely necessary to bring out the true clinical potential of TCVs.

scholarly journals Immunotherapies in Genitourinary Oncology: Where Are We Now? Where Are We Going?

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5065
Author(s):  
Albert Jang ◽  
David M. Adler ◽  
Grant P. Rauterkus ◽  
Mehmet A. Bilen ◽  
Pedro C. Barata
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
The United States ◽  
The Past ◽  
United States Food ◽  
States Food ◽  
Genitourinary Cancers ◽  
Tumor Types

For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

Positivity of serum “classical” onconeural antibodies in a series of 2063 consecutive patients with suspicion of paraneoplastic neurological syndrome

2013 ◽  
Vol 259 (1-2) ◽  
pp. 75-80 ◽  
Author(s):  
Grażyna Gromadzka ◽  
Anna G. Karlińska ◽  
Zofia Łysiak ◽  
Beata Błażejewska-Hyżorek ◽  
Tomasz Litwin ◽  
...  
Keyword(s):  
Paraneoplastic Neurological Syndrome ◽  
Neurological Syndrome ◽  
Onconeural Antibodies

scholarly journals Microbiome and Cancer Immunotherapy

2021 ◽  
Vol 96 (4) ◽  
pp. 312-317
Author(s):  
Moonki Hong ◽  
Minkyu Jung
Keyword(s):  
Checkpoint Inhibitors ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Clinical Results ◽  
Genome Project ◽  
Human Diseases ◽  
The Past ◽  
Preclinical And Clinical Studies ◽  
Tumor Types ◽  
The Relationship

Immune checkpoint inhibitors (ICIs) have achieved promising clinical results in cancer treatment over the past decade. However, the efficacy of ICIs is less than 30% in most tumor types, and studies are underway to identify the predictive factors responsive to ICIs. More than 1,000 species of microorganisms live in the human body, and the second human genome project, The Human Microbiome Project, has been conducted to understand human diseases through interactions with microbes. As the microbiome project has progressed, many studies have reported on the association between microorganisms and human diseases, including preclinical and clinical studies on the relationship between ICIs and the microbiome. Therefore, in this manuscript, the relationship between the microbiome and cancer, especially the effectiveness of ICIs, is reviewed.

Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

2019 ◽  
Vol 19 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Qihui Wu ◽  
Hanzhong Ke ◽  
Dongli Li ◽  
Qi Wang ◽  
Jiansong Fang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Large Scale ◽  
Recent Progress ◽  
High Specificity ◽  
Learning Approaches ◽  
Anticancer Peptides ◽  
The Past ◽  
Traditional Approaches ◽  
Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

scholarly journals Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 678 ◽  
Author(s):  
Adrien Procureur ◽  
Audrey Simonaggio ◽  
Jean-Emmanuel Bibault ◽  
Stéphane Oudard ◽  
Yann-Alexandre Vano
Keyword(s):  
Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Mitotic Cell ◽  
Immunogenic Cell Death ◽  
Dna Damages ◽  
Multiple Tumor ◽  
Tumor Types

The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Index ◽  
Predictive Marker ◽  
Risk Groups ◽  
Two Factors ◽  
One Year ◽  
Metastatic Sites ◽  
Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

scholarly journals What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Yu Yao ◽  
Heng Liang ◽  
Xin Fang ◽  
Shengnan Zhang ◽  
Zikang Xing ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Kynurenine Pathway ◽  
Phase Iii ◽  
Current Status ◽  
The Past ◽  
Indoleamine 2,3 Dioxygenase ◽  
Negative Results ◽  
Rate Limiting Step ◽  
Pharmacodynamic Markers ◽  
Tumor Types

AbstractIndoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.

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