Combining Chemotherapy with Immunotherapy in Colorectal Cancer: A Review

2020 ◽  
Vol 07 ◽  
Author(s):  
John Thomas Palathingal ◽  
Basil Sunny ◽  
Vismaya Vijayan
Keyword(s):  
Colorectal Cancer ◽  
Time Window ◽  
Positive Impact ◽  
Combined Treatment ◽  
Treatment Algorithm ◽  
Treatment Modalities ◽  
Cancer Society ◽  
Treatment Techniques ◽  
Comprehensive Knowledge

Abstract:: American Cancer Society estimates that about 1 in 21 men and 1 in 23 women in US will develop colorectal cancer during their lifetime. Due to the advances in screening and treatment modalities, the mortality rate has reduced. Rising resistance to treatment have directed the focus towards different approaches as combination therapies involving different treatment techniques available. One such approach is chemo-immunotherapy that targets to modulate TIME and improve the response to immunotherapy. The chemo-immunotherapy has shown a positive impact in improving the outcome of CRC treatment. The ensemble of results discussed herein supports the role of biomarkers in determining the most effective treatment algorithm. A comprehensive knowledge about the off-target effects of the cytotoxic drugs helps in designing more efficacious combined treatment. The time-window for optimal combination must also be considered carefully.

scholarly journals Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1857
Author(s):  
Sahar Al Kattar ◽  
Rosalyn Jurjus ◽  
Aline Pinon ◽  
David Yannick Leger ◽  
Abdo Jurjus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Process ◽  
Colorectal Carcinogenesis ◽  
Treatment Modalities ◽  
Downstream Signaling ◽  
Diabetes In Mice ◽  
Tnf Α ◽  
Shed Light

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6–8 weeks old, were divided into 16 control and experimental groups to assess the effect of the different treatments and combinations at the clinical, histological, and molecular levels. Metformin and probiotics showed beneficial outcomes on CRC and diabetes, alone and most importantly in combination. Their effects were exerted by inhibiting the inflammatory process whereby a downregulation of IL-6 and TNF-α as well as oxidative stress were depicted. The characterization of the effects of probiotics and metformin on CRC and diabetes sheds light on the role of inflammation and microbiota in this crosstalk. Deciphering the downstream signaling pathways elicited by these compounds will help in developing new effective targeted treatment modalities.

Posterior Tibial Artery Pseudoaneurysm with Arteriovenous Fistula: Impact of Duplex Ultrasound on Diagnosis and Treatment

2017 ◽  
Vol 41 (1) ◽  
pp. 31-35
Author(s):  
Keith Himes ◽  
Amanda Bornais ◽  
Emelia Bittenbinder ◽  
Judith Cook
Keyword(s):  
Treatment Algorithm ◽  
Duplex Ultrasound ◽  
Posterior Tibial Artery ◽  
Diagnosis And Treatment ◽  
Treatment Modalities ◽  
Artery Pseudoaneurysm ◽  
Post Traumatic ◽  
Orthopedic Injuries ◽  
Venous Fistula

Post traumatic peripheral vascular injuries resulting in pseudoaneurysm (PSA) or arterial venous fistula (AVF) are rarely reported and may occur independently, or less commonly, concomitantly, following lower extremity fractures, penetrating or blunt trauma, and sports-related or orthopedic injuries. 1 Concomitant traumatic PSA and AVF requires accurate imaging and evaluation of hemodynamics for accurate diagnosis and treatment. Modalities for PSA repair include ultrasound-guided occlusion (thrombin injection), endovascular repair (coils, stents), and open surgical procedures (repair, ligation). A coexisting AVF can potentially impact the efficacy and safety of these options. This case demonstrates the important role of duplex ultrasound in the diagnosis and treatment algorithm of traumatic PSA.

scholarly journals Potential Role of the Gut Microbiome In Colorectal Cancer Progression

2022 ◽  
Vol 12 ◽  
Author(s):  
Jaeho Kim ◽  
Heung Kyu Lee
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Cancer Treatment ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Treatment Modalities ◽  
Host Immune System ◽  
Anti Cancer

An increasing number of studies have revealed that the progression of colorectal cancer (CRC) is related to gut microbiome composition. Under normal conditions, the gut microbiome acts as a barrier to other pathogens or infections in the intestine and modulates inflammation by affecting the host immune system. These gut microbiota are not only related to the intestinal inflammation associated with tumorigenesis but also modulation of the anti-cancer immune response. Thus, they are associated with tumor progression and anti-cancer treatment efficacy. Studies have shown that the gut microbiota can be used as biomarkers to predict the effect of immunotherapy and improve the efficacy of immunotherapy in treating CRC through modulation. In this review, we discuss the role of the gut microbiome as revealed by recent studies of the growth and progression of CRC along with its synergistic effect with anti-cancer treatment modalities.

scholarly journals The role of combined treatment of metastatic colorectal cancer in patients with liver metastases

2019 ◽  
Vol 30 ◽  
pp. iv55
Author(s):  
D. Gridnev ◽  
M. Trandofilov ◽  
A. Zhevelyuk ◽  
D. Islamova ◽  
V. Makarov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Combined Treatment

Use of Surgery Among Elderly Patients With Stage IV Colorectal Cancer

2004 ◽  
Vol 22 (17) ◽  
pp. 3475-3484 ◽  
Author(s):  
Larissa K.F. Temple ◽  
Lillian Hsieh ◽  
W. Douglas Wong ◽  
Leonard Saltz ◽  
Deborah Schrag
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Postoperative Mortality ◽  
Stage Iv ◽  
Population Based ◽  
Treatment Modalities ◽  
Medicare Beneficiaries ◽  
Stage Iv Colorectal Cancer ◽  
Lower Socioeconomic

Purpose The role of surgery to remove the primary tumor among patients with stage IV colorectal cancer (CRC) is controversial. The purpose of this study was to evaluate surgical practice patterns for patients ≥ 65 years of age with stage IV CRC in a US population-based cohort. Patients and Methods We used the Surveillance, Epidemiology, and End Results-Medicare–linked database to evaluate the patterns of cancer treatment for 9,011 Medicare beneficiaries presenting with stage IV CRC from 1991 to 1999. Patients were categorized according to whether they had primary–cancer-directed surgery (CDS) or no CDS within 4 months of diagnosis. The use of other treatment modalities, including metastasectomy, chemotherapy, and radiation, was evaluated in relationship to whether patients belonged to the CDS or no CDS group. Results Seventy-two percent (6,469 of 9,011) of patients received CDS, and their 30-day postoperative mortality was 10%. Patients with left-sided or rectal lesions, patients older than age 75 years, blacks, and those of lower socioeconomic status were less likely to undergo CDS; but even among those older than age 75, the CDS rate was 69% (3,378 of 4,909). In contrast, chemotherapy use was less common (47% for patients who had CDS and 31% for those who did not). Metastasectomy was rare; only 3.9% of patients underwent these operations at any point from diagnosis to death. Conclusion Palliative resection of the primary tumor is often performed for elderly US patients with stage IV colorectal cancer. This practice pattern merits re-evaluation, given the improvement in the efficacy of systemic chemotherapy.

scholarly journals Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 743
Author(s):  
Da-Young Lee ◽  
Moon-Young Song ◽  
Eun-Hee Kim
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Inflammatory Diseases ◽  
Negative Regulator ◽  
Related Factor ◽  
Cancer Society ◽  
Incidence And Mortality

Colorectal cancer still has a high incidence and mortality rate, according to a report from the American Cancer Society. Colorectal cancer has a high prevalence in patients with inflammatory bowel disease. Oxidative stress, including reactive oxygen species (ROS) and lipid peroxidation, has been known to cause inflammatory diseases and malignant disorders. In particular, the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. Nrf2 was first found in the homolog of the hematopoietic transcription factor p45 NF-E2, and the transcription factor Nrf2 is a member of the Cap ‘N’ Collar family. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. Therefore, the discovery of phytochemicals regulating the Nrf2/KEAP1 axis and verification of their efficacy have attracted scientific attention. In this review, we summarize the role of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer.

scholarly journals Diversity and Distribution of Sulfur Metabolism 1 in the Human Gut Microbiome and its Association with Colorectal Cancer

2021 ◽  
Author(s):  
Patricia G. Wolf ◽  
Elise S. Cowley ◽  
Adam Breister ◽  
Sarah Matatov ◽  
Luke Lucio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sulfate Reduction ◽  
Gut Microbiome ◽  
Sulfur Metabolism ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Metabolic Genes ◽  
Comprehensive Knowledge ◽  
Potential Trigger

Abstract Background: Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human gut using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates, however the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr). Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut.Results: Here we show that microbial sulfur metabolism is more abundant and diverse than previously studied and is statistically associated with CRC. Using ~17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, anaerobic sulfite reductases were twice as abundant as dsr, demonstrating that this enzyme is likely a more important contributor to sulfate reduction in the human gut. We identified twelve potential pathways for reductive taurine metabolism and discovered novel genera harboring these pathways. Finally, prevalence of metabolic genes for organic sulfur indicate that these understudied substrates may be the most abundant source of microbially derived H2S.Conclusions: Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut. We show that microbial sulfur metabolism in the human gut is more prevalent than previously known, irrespective of health status (i.e., in both healthy and diseased states). Our results significantly increase the diversity of pathways and bacteria that are associated with microbial sulfur metabolism in the human gut. Overall, our results have implications for understanding the role of the human gut microbiome and its potential contributions to the pathogenesis of CRC.

scholarly journals RRAD expression in gastric and colorectal cancer with peritoneal carcinomatosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hee Kyung Kim ◽  
Inkyoung Lee ◽  
Seung Tae Kim ◽  
Jeeyun Lee ◽  
Kyoung-Mee Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Combined Treatment ◽  
Cancer Tissue ◽  
Associated Proteins ◽  
Emt Markers

AbstractThe role of Ras-related associated with diabetes (RRAD) in gastric cancer (GC) or colorectal cancer (CRC) has not been investigated. We aimed to investigate the biological and clinical roles of RRAD in GC and CRC and to assess RRAD as a therapeutic target. A total of 31 cancer cell lines (17 GC cell lines, 14 CRC cell lines), 59 patient-derived cells (PDCs from 48 GC patients and 11 CRC patients), and 84 matched pairs of primary cancer tissue and non-tumor tissue were used to evaluate the role of RRAD in vitro and in vivo. RRAD expression was frequently increased in GC and CRC cell lines, and siRNA/shRNA-mediated RRAD inhibition induced significant decline of tumor cell proliferation both in vitro and in vivo. A synergistic effect of RRAD inhibition was generated by combined treatment with chemotherapy. Notably, RRAD expression was markedly increased in PDCs, and RRAD inhibition suppressed PDC proliferation. RRAD inhibition also resulted in reduced cell invasion, decreased expression of EMT markers, and decreased angiogenesis and levels of associated proteins including VEGF and ANGP2. Our study suggests that RRAD could be a novel therapeutic target for treatment of GC and CRC, especially in patients with peritoneal seeding.

scholarly journals Cautious optimism—the current role of immunotherapy in gastrointestinal cancers

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
S. Mendis ◽  
S. Gill
Keyword(s):  
Colorectal Cancer ◽  
Phase Iii ◽  
Treatment Modalities ◽  
Checkpoint Inhibition ◽  
Phase Ii Trials ◽  
Gastrointestinal Tumours ◽  
Phase Iii Trials ◽  
Combined Positive Score ◽  
Line Setting

Immunotherapy has been described as the “fourth pillar” of oncology treatment, in conjunction with surgery, chemotherapy, and radiotherapy. However, the role of immunotherapy in gastrointestinal tumours is still evolving. Data for checkpoint inhibition in esophagogastric, hepatocellular, colorectal, and anal squamous cell carcinomas are expanding. In phase iii trials in the second-line setting, PD-1 inhibitors have demonstrated positive results for the subset of esophageal cancers that are positive for PD-L1 at a combined positive score of 10 or more. Based on results of phase ii trials, PD-1 inhibitors were approved in North America for use in PD-L1–positive chemorefractory gastric cancers, in hepatocellular carcinoma after sorafenib exposure, and in treatment refractory deficient mismatch repair (dmmr) or high microsatellite instability (msi-h) tumours, regardless of tissue site. Combination use of PD-1 and ctla-4 inhibitors has been approved by the U.S. Food and Drug Administration for chemorefractory dmmr or msi-h colorectal cancer. Responses to checkpoint inhibition are durable, particularly in the dmmr or msi-h colorectal cancer cohort. As trials of combination immunotherapy, immunotherapy in combination with other systemic therapies, and immunotherapy in combination with other treatment modalities move forward in multiple tumour sites, cautious optimism is called for. The treatment landscape is continually changing, and expanded indications are likely to be just around the corner.

scholarly journals Immune-Modulating Effects of Conventional Therapies in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2193
Author(s):  
Erta Kalanxhi ◽  
Sebastian Meltzer ◽  
Anne Hansen Ree
Keyword(s):  
Colorectal Cancer ◽  
Immune Therapy ◽  
Standard Of Care ◽  
Cytotoxic Agents ◽  
Treatment Modalities ◽  
New Developments ◽  
Adaptive Immune ◽  
Small Subgroup ◽  
Tumor Dissemination

Biological heterogeneity and low inherent immunogenicity are two features that greatly impact therapeutic management and outcome in colorectal cancer. Despite high local control rates, systemic tumor dissemination remains the main cause of treatment failure and stresses the need for new developments in combined-modality approaches. While the role of adaptive immune responses in a small subgroup of colorectal tumors with inherent immunogenicity is indisputable, the challenge remains in identifying the optimal synergy between conventional treatment modalities and immune therapy for the majority of the less immunogenic cases. In this context, cytotoxic agents such as radiation and certain chemotherapeutics can be utilized to enhance the immunogenicity of an otherwise immunologically silent disease and enable responsiveness to immune therapy. In this review, we explore the immunological characteristics of colorectal cancer, the effects that standard-of-care treatments have on the immune system, and the opportunities arising from combining immune checkpoint-blocking therapy with immune-modulating conventional treatments.

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