Drug-Related Pneumonitis in the Era of Precision Cancer Therapy

Drug-related pneumonitis as a result of novel cancer therapy provides new challenges for providers of cancer care in the era of precision medicine. Awareness of this emerging entity and knowledge of its manifestations and management guidelines are essential for state-of-the-art practice of clinical oncology. Here, we provide a detailed review of drug-related pneumonitis that develops during precision cancer therapies using immune-checkpoint inhibitors and molecular targeting agents, and we summarize the emerging data that have been obtained by recent investigations to provide a state-of-the-art overview for clinicians involved in cancer care. We focus on immune-checkpoint inhibitor–related pneumonitis, which is an immune-related adverse event of growing interest and increasing clinical significance in current oncology practice that has rapidly expanding access to these agents. Clinical characteristics, radiographic spectrum, and risk factors and outcome of pneumonitis are described for each class of agents, and current treatment guidelines and monitoring recommendations are discussed. This review also indicates the area of unmet clinical need and provides direction for future investigations, as well as emphasizing the importance of a multidisciplinary approach to further understand the mechanisms, develop methods for accurate diagnosis, and optimize management guidelines of drug-related pneumonitis in the era of precision oncology.

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DeepGeni: Deep generalized interpretable autoencoder elucidates gut microbiota for better cancer immunotherapy

10.1101/2021.05.06.443032 ◽

2021 ◽

Author(s):

Min Oh ◽

LIQING ZHANG

Keyword(s):

Machine Learning ◽

Gut Microbiota ◽

Cancer Immunotherapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

State Of The Art ◽

Checkpoint Inhibitors ◽

Precision Oncology ◽

Learning Classifier ◽

Melanoma Patients

Recent studies revealed that gut microbiota modulates the response to cancer immunotherapy and fecal microbiota transplantation has clinical benefit in melanoma patients during the treatment. Understanding microbiota affecting individual response is crucial to advance precision oncology. However, it is challenging to identify the key microbial taxa with limited data as statistical and machine learning models often lose their generalizability. In this study, DeepGeni, a deep generalized interpretable autoencoder, is proposed to improve the generalizability and interpretability of microbiome profiles by augmenting data and by introducing interpretable links in the autoencoder. DeepGeni-based machine learning classifier outperforms state-of-the-art classifier in the microbiome-driven prediction of responsiveness of melanoma patients treated with immune checkpoint inhibitors. DeepGeni-based machine learning classifier outperforms state-of-the-art classifier in the microbiome-driven responsiveness prediction of melanoma patients treated with immune checkpoint inhibitors. Also, the interpretable links of DeepGeni elucidate the most informative microbiota associated with cancer immunotherapy response.

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Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211024460 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110244

Author(s):

Vanessa Wookey ◽

Axel Grothey

Keyword(s):

Colorectal Cancer ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Standard Of Care ◽

Cancer Type ◽

Cancer Therapies ◽

Multiple Cancer ◽

Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

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Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

International Journal of Molecular Sciences ◽

10.3390/ijms22010190 ◽

2020 ◽

Vol 22 (1) ◽

pp. 190

Author(s):

Fulvio Borella ◽

Mario Preti ◽

Luca Bertero ◽

Giammarco Collemi ◽

Isabella Castellano ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

State Of The Art ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Survival Rates ◽

Younger Women ◽

Multiple Tumor ◽

Tumor Types

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

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Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

Digestion ◽

10.1159/000518543 ◽

2021 ◽

pp. 1-9

Author(s):

Shunichi Yanai ◽

Yosuke Toya ◽

Tamotsu Sugai ◽

Takayuki Matsumoto

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Malignant Tumors ◽

Checkpoint Inhibitors ◽

Architectural Distortion ◽

Management Guidelines ◽

Crypt Abscess ◽

Gastrointestinal Adverse Events ◽

Histopathologic Findings

Background: As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. Summary: Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. Key Messages: Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

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Pharmacokinetics and Systems Pharmacology of Anti-CD47 Macrophage Immune Checkpoint Inhibitor Hu5F9-G4

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117666190820105134 ◽

2020 ◽

Vol 17 (1) ◽

pp. 14-24 ◽

Cited By ~ 1

Author(s):

Adarsh Mishra ◽

Ishant Kataria ◽

Sujit Nair

Keyword(s):

Annual Meeting ◽

Immune Checkpoint ◽

Cancer Care ◽

Checkpoint Inhibitors ◽

B Cell Lymphoma ◽

Great Promise ◽

Systems Pharmacology ◽

Immunoglobulin G4 ◽

American Society ◽

Anti Cd20

Background: Hu5F9-G4, a human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) has recently been granted fast-track designation by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Hu5F9-G4 has the ability to block CD47-SIRPα signaling along with anti- EGFR and anti-PD-L1 immune checkpoint activity that is involved in a variety of cancers like solid tumors, Non-Hodgkin’s Lymphoma (NHL), colorectal cancer (CRC), breast, ovarian and bladder cancers, and hematological malignancies. Thus, Hu5F9-G4 is an important biologic that has increasing clinical relevance in cancer care. Methods: We queried PubMed, Web of Science, Google Scholar, Science Direct and Scopus databases with keywords pertaining to Hu5F9-G4. In addition, we have included the Hu5F9-G4 data presented at the 60th American Society of Hematology (ASH) Annual Meeting, the American Society of Clinical Oncology (ASCO) Annual Meeting and 23rd Congress of the European Hematology Association (EHA). Results: We discuss the mechanistic basis and preclinical evidence for the anticancer activity of Hu5F9-G4. Further, we delineate clinical studies, alone and in combination with anti-CD20 mAb rituximab, anti-EGFR mAb cetuximab, PD-L1 checkpoint inhibitors avelumab and atezolizumab, and anti-HER2 mAb trastuzumab. Moreover, the potential adverse effects, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 with emphasis on the role of CD47-SIRPα signaling in phagocytosis are presented. Conclusions: Taken together, we review the pharmacokinetics and systems pharmacology of Hu5F9-G4 which appears to hold great promise for the future of cancer care.

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Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms21207575 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7575 ◽

Cited By ~ 1

Author(s):

Shruti S. Sawant ◽

Suyash M. Patil ◽

Vivek Gupta ◽

Nitesh K. Kunda

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Treatment Options ◽

Current Treatment ◽

Genetically Engineered ◽

Cancer Therapies ◽

Anti Cancer ◽

Tumor Environment ◽

Systemic Side Effects ◽

Hypoxic Tumor

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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Targeted Cancer Therapies With Pericardial Effusions Requiring Pericardiocentesis Focusing on Immune Checkpoint Inhibitors

The American Journal of Cardiology ◽

10.1016/j.amjcard.2019.01.013 ◽

2019 ◽

Vol 123 (8) ◽

pp. 1351-1357 ◽

Cited By ~ 10

Author(s):

Nicolas Palaskas ◽

Jacob Morgan ◽

Tina Daigle ◽

Jose Banchs ◽

Jean-Bernard Durand ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Therapies ◽

Pericardial Effusions ◽

Targeted Cancer Therapies

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Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells, by Varun Sasidharan Nair and Eyad Elkord (Erratum)

Immunology and Cell Biology ◽

10.1111/imcb.12012 ◽

2018 ◽

Vol 96 (2) ◽

pp. 236-236

Keyword(s):

Cancer Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

T Regulatory Cells ◽

Checkpoint Inhibitors ◽

Regulatory Cells

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Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies

International Journal of Molecular Sciences ◽

10.3390/ijms20020341 ◽

2019 ◽

Vol 20 (2) ◽

pp. 341 ◽

Cited By ~ 8

Author(s):

Dik-Lung Ma ◽

Chun Wu ◽

Sha-Sha Cheng ◽

Fu-Wa Lee ◽

Quan-Bin Han ◽

...

Keyword(s):

Side Effects ◽

Cancer Therapy ◽

Adverse Effects ◽

Metal Complexes ◽

Natural Product ◽

Cancer Care ◽

Cancer Therapies ◽

The Future ◽

Therapy Development ◽

Enhanced Selectivity

Platinum-based drugs have revolutionized cancer care, but are unfortunately associated with various adverse effects. Meanwhile, natural product scaffolds exhibit multifarious bioactivities and serve as an attractive resource for cancer therapy development. Thus, the conjugation of natural product scaffolds to metal complexes becomes an attractive strategy to reduce the severe side effects arising from the use of metal bearing drugs. This review aims to highlight the recent examples of natural product-conjugated metal complexes as cancer therapies with enhanced selectivity and efficacy. We discuss the mechanisms and features of different conjugate complexes and present an outlook and perspective for the future of this field.

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