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

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.

scholarly journals Recent advances in understanding colorectal cancer

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1528 ◽  
Author(s):  
Sebastian Stintzing
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Molecular Testing ◽  
Effective Treatment Option ◽  
Chemotherapy Study

The achievements in the treatment of metastatic colorectal cancer during recent years are based on a better understanding of the disease and individualized regimen planning. In adjuvant treatment, the highly important IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study has shown that treatment duration can safely be reduced in selected patient populations. In patients with pN1 and pT1-pT3 tumors, 3 months of treatment with 5-fluorouracil and oxaliplatin is comparable with respect to 3-year survival rate to 6 months of treatment. For patients with N2 tumors, 6 months of treatment should stay the standard of care. The limitation of the duration of the adjuvant treatment is significantly reducing the chemotherapy-induced morbidity. New studies will explore the use of immune-checkpoint inhibitors in the adjuvant setting in microsatellite-instable (MSI) tumors. In metastatic disease, next to the required molecular testing for RAS and BRAF mutations, MSI testing is recommended. In the rare group of patients with a MSI tumor, immune-checkpoint inhibition is changing the course of the disease dramatically. Therefore, it is important to identify those patients early. For the RAS-mutant cases, no new and targeted treatment options have been identified yet. An optimal treatment strategy for those patients is urgently needed. RAS wild-type patients with tumors derived from the left side of the colon (splenic flexure to rectum) should be treated in first line with epithelial growth factor receptor (EGFR) antibodies. This selection by a molecular and a clinical marker increased the benefit derived by EGFR antibodies dramatically and defined the most effective treatment option for those patients. New selection criteria based on gene expression, methylation, and other molecular changes are explored and will further influence our therapeutic strategies in the future.

Nanotechnology-based platforms to improve immune checkpoint blockade efficacy in cancer therapy

2020 ◽  
Author(s):  
Deeksha G Lahori ◽  
Pegah Varamini
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Standard Of Care Treatment ◽  
Anticancer Treatment ◽  
Novel Strategy

In recent years, cancer immunotherapy has evolved as an exciting novel strategy for researchers and clinicians worldwide. Immunotherapeutic agents such as immune checkpoint blockers have changed the standard-of-care treatment provided for many tumors. Unfortunately, only a small proportion of patients respond effectively to these checkpoint inhibitors. Moreover, the immunosuppressive pathways for cancer are probably too complicated to achieve optimal outcome with immune checkpoint inhibitors alone. Combining current therapeutic options and immunotherapy-based approaches is being explored as an effective strategy to treat cancer. The use of nanotechnology-based platforms for delivery of immunotherapeutic agents or combination therapy could offer a major advantage over conventional anticancer treatment options. This review highlights the potential role of different nanotechnology-based strategies in improving the efficacy of immune checkpoint blockade therapy.

scholarly journals Cancer associated-fibroblast-derived exosomes in cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Li ◽  
Adilson Fonseca Teixeira ◽  
Hong-Jian Zhu ◽  
Peter ten Dijke
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP NENs) : The Role of Checkpoint Inhibitors

2022 ◽  
Vol 22 ◽  
Author(s):  
Giulia Arrivi ◽  
Nicola Fazio
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Response Assessment ◽  
Neuroendocrine Neoplasms ◽  
Precision Oncology ◽  
Disease Characteristics

Background: The treatment options for GEP-NENs includes various drugs and is based on grading, morphology and location of the primary Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs. Method: A scientific literature search from 2015 to January 2020 was performed by using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included Results: several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays the current knowledge in this field is mainly based on a phase I-II studies. Immunotherapy showed limited antitumor activity, but higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays we see many gaps in this field. We must balance therapeutic possibility offered by precision oncology with the understanding the limitations of application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to candidate for immunotherapy in term of disease characteristics and previous treatments, and how to select them with accurate biomarkers.

scholarly journals The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

2022 ◽  
Vol 12 ◽  
Author(s):  
Huan Tong ◽  
He Wei ◽  
Alhaji Osman Smith ◽  
Juan Huang
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Epigenetic Modification ◽  
Advanced Malignancy ◽  
Tumor Drug Resistance ◽  
New Strategies

Tumor immunotherapy, one of the efficient therapies in cancers, has been called to the scientific community’s increasing attention lately. Among them, immune checkpoint inhibitors, providing entirely new modalities to treat cancer by leveraging the patient’s immune system. They are first-line treatments for varieties of advanced malignancy, such as melanoma, gastrointestinal tumor, esophageal cancer. Although immune checkpoint inhibitors (ICIs) treatment has been successful in different cancers, drug resistance and relapses are common, such as in colorectal cancer. Therefore, it is necessary to improve the efficacy of immune checkpoint therapy for cancer patients who do not respond or lowly response to current treatments. N6-methyladenosine (m6A), as a critical regulator of transcript expression, is the most frequently internal modification of mRNA in the human body. Recently, it has been proposed that m6A epigenetic modification is a potential driver of tumor drug resistance. In this report, we will briefly outline the relevant mechanisms, general treatment status of immune checkpoint inhibitors in colorectal cancer, how m6A epigenetic modifications regulate the response of ICIs in CRC and provide new strategies for overcoming the resistance of ICIs in CRC.

scholarly journals Current status and perspectives of immune checkpoint inhibitors for colorectal cancer

2020 ◽  
Vol 51 (1) ◽  
pp. 10-19
Author(s):  
Hidekazu Hirano ◽  
Atsuo Takashima ◽  
Tetsuya Hamaguchi ◽  
Dai Shida ◽  
Yukihide Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
High Level ◽  
Deficient Mismatch Repair

Abstract Immunotherapy, especially immune checkpoint inhibitors, has revolutionized the standard-of-care of multiple types of tumors. For colorectal cancer, the clinical development of immune checkpoint inhibitors is mainly separated according to the status of microsatellite instability or mismatch repair in a tumor. High-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer generally has a tumor microenvironment with infiltration of T cells, associated with a favorable response to immune checkpoint inhibitors. Immune checkpoint inhibitors, including pembrolizumab (anti-PD-1 inhibitor) and nivolumab (anti-PD-1 inhibitor) with or without ipilimumab (anti-CTLA-4 inhibitor), have been integrated into the standard-of-care for high-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer. Conversely, limited T-cell infiltration in the tumor microenvironment of microsatellite stable/proficient mismatch repair metastatic colorectal cancer, which constitutes the majority of metastatic colorectal cancer, is assumed to be a major resistant mechanism to immune checkpoint inhibitors. Currently, clinical trials to improve the clinical activity of immune checkpoint inhibitors by immunomodulation are ongoing for metastatic colorectal cancer. Furthermore, immune checkpoint inhibitors are under development in neoadjuvant and/or adjuvant setting. Here, we review the existing clinical data with ongoing trials and discuss the future perspectives with a focus on the immunotherapy of colorectal cancer.

scholarly journals The Role of Immunotherapy in the Treatment of Adrenocortical Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 98
Author(s):  
Izabela Karwacka ◽  
Łukasz Obołończyk ◽  
Sonia Kaniuka-Jakubowska ◽  
Krzysztof Sworczak
Keyword(s):  
Immune Checkpoint ◽  
Adrenocortical Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Distant Metastases ◽  
Immune Checkpoints ◽  
High Tendency

Adrenocortical carcinoma (ACC) is a rare epithelial neoplasm, with a high tendency for local invasion and distant metastases, with limited treatment options. Surgical treatment is the method of choice. For decades, the mainstay of pharmacological treatment has been the adrenolytic drug mitotane, in combination with chemotherapy. Immunotherapy is the latest revolution in cancer therapy, however preliminary data with single immune checkpoint inhibitors showed a modest activity in ACC patients. The anti-neoplastic activity of immune checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated-antigen 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-ligand-1 (PD-L1) antibodies in different solid tumors has aroused interest to explore the potential therapeutic effect in ACC as well. Multiple ongoing clinical trials are currently evaluating the role of immune checkpoint inhibitors in ACC (pembrolizumab, combination pembrolizumab and relacorilant, nivolumab, combination nivolumab and ipilimumab). The primary and acquired resistance to immunotherapy continue to counter treatment efficacy. Therefore, attempts are made to combine therapy: anti-PD-1 antibody and anti-CTLA-4 antibody, anti-PD-1 antibody and antagonist of the glucocorticoid receptor. The inhibitors of immune checkpoints would benefit patients with antitumor immunity activated by radiotherapy. Immunotherapy is well tolerated by patients; the most frequently observed side effects are mild. The most common adverse effects of immunotherapy are skin and gastrointestinal disorders. The most common endocrinopathy during anti-CTLA treatment is pituitary inflammation and thyroid disorders.

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