Important link identified between the immune response and colon tumor formation
“We have been trying for the past several years to understand the precise links between inflammation and cancer,” comments Ray Dubois, Arizona State University (AZ, USA). “We have demonstrated that CXCR2 mediates a critical step in the setup of the blood circulatory machinery that feeds tumor tissue. This provides an important new clue for the development of therapeutic targets to neutralize the effect of CXCR2 on colon cancer.”
Colorectal cancer is the second leading cause of cancer deaths in the USA and has a low 5-year survival rate. Many patients present with the disease at an advanced stage despite the fact that colonoscopy screening is readily available. There are currently no other tests for the early detection of colorectal cancers.
Chronic inflammation is a known contributor to cancer initiation and development, particularly colon cancer, as drugs such as aspirin are recognized to decrease the risk of developing this type of cancer. DuBois, lead researcher of the study published in Cancer Cell, and colleagues from Arizona State University identified a key genetic factor in the formation, progression and growth of tumors in a mouse model of colon cancer.
The researchers began by removing the CXCR2 gene from mice. This gene encodes CXCR2, which presents on the surface of myeloid-derived suppressor cells, which block the immune response of killer CD8+ T cells. When the CXCR2 gene was removed, the mice presented reduced signs of inflammation and suppressed colitis-associated tumor development. This is believed to be due to the myeloid-derived suppressor cells being prevented from migrating into the colon from the circulation; therefore, avoiding the blood supply of the tumor environment and the T-cell immune response. This conclusion was further clarified by transplanting myeloid-derived suppressor cells with CXCR2 into the knockout mice, which restored tumor formation.
This news highlights the importance of the inflammatory pathway in colorectal cancer development and progression. The results demonstrate a key link that may lead to the future development of novel therapeutic approaches and enhance our understanding of the interaction between the immune system and tumor formation.
DuBois concludes, “Our findings rezow myeloid-derived suppressor cells are recruited to local inflamed tissues and tumor microenvironment and how local myeloid-derived suppressor cells contribute to colorectal cancer progression, but now also provide rationale for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression by using CXCR2 antagonists and neutralizing antibodies.”
– Written by Elizabeth Webb Illustrated by Amy O‘Donnell
Source: Arizona State University press release: https://asunews.asu.edu/20131111-DuBois-colon-cancer
Recurrence risk of colorectal adenoma increases with increased sedentary behavior
Results presented recently at the 12th Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research (MD, USA) suggest a link between a sedentary lifestyle and the risk of colorectal cancer recurrence. Although there is extensive evidence supporting the association of an active lifestyle and reduced risk of colorectal cancer, very little research has focused on the role of sedentary behavior in the risk of colorectal cancer. Christine Sardo Molmenti and colleagues at Columbia University‘s Mailman School of Public Health (NY, USA) performed a pooled analysis of participants of two previous randomized, double-blind, placebo-controlled Phase III clinical trials to further investigate this matter.
“Sedentary behavior is emerging as a risk factor for poor health. Even among those who fulfill daily recommendations for physical activity, lengthy periods of sedentary behavior have been associated with early morbidity and mortality, leading to the ‘active couch potato‘ paradigm,” commented Sardo Molmenti. “To our knowledge, this study is the first to specifically investigate the association between sedentary behavior and recurrence of colorectal adenomas.”
Colorectal adenomas or colorectal adenomatous polyps are benign tumors of the colon and known precursors of colorectal cancer, which can be removed via colonoscopy. This analysis, performed by Sardo Molmenti and colleagues, comprised patients who had one or more colorectal adenomas removed 6 months prior to their enrollment. Included in this cohort were 1730 participants who had undergone a follow-up colonoscopy and had completed a self-administered questionnaire, which consisted of questions on basic activities including leisure, recreational and household activities.
Analysis of all data demonstrated no association between the type of activity and colorectal adenoma recurrence. However, on stratifying the data by sex they discovered that men who engaged in more than 11.38 h of sedentary activity daily (e.g., reading, writing, typing or working at a computer) were 45% more likely to experience a colorectal adenoma recurrence compared with men who spent less than 6.90 h a day engaging in sedentary activities. Furthermore, men who reported high levels of sedentary behavior and low participation in recreational activities (e.g., walking, jogging or playing golf) were 41% more likely to experience a recurrence compared with men reporting higher levels of activity. There was no association observed between sedentary time and colorectal adenoma recurrence for women.
“Given the substantial increase in risk of colorectal adenoma recurrence we observed for men with the highest sedentary time, we believe it would be beneficial to see ‘reduce prolonged sitting time‘ added to the list of public health recommendations currently in place for health promotion and disease prevention,” concludes Sardo Molmenti. Moreover, she believes that this increase in risk confirms that sedentary behavior appears to independently contribute to increased cancer risk beyond the accompanying reduction in physical activity. In order to further elucidate the role of sedentary behavior in the risk of cancer, new tools and techniques are required to better classify and quantify sedentary behaviors.
– Written by Janet Lee
Source: Columbia University, Mailman School of Public Health press release: www.mailman.columbia.edu/news/mailman-school-researcher-presents-paper-aacr-conference-link-between-sedentary-behavior-and-re
Genetic changes in the lining of the colon to identify colorectal cancer?
A study published online recently in Cancer Prevention Research has identified novel genetic changes that are present in the lining of the colon of individuals suffering from colorectal cancer. The researchers postulate that these changes may represent diagnostic biomarkers of colorectal cancer and could ease the process of diagnosing these malignancies in patients; a process that is currently complex and invasive. “The gold standard of diagnosis is currently colonoscopy,” explained corresponding author of the study Rima Rozen, a geneticist from McGill University (QC, Canada) where the study was carried out. “This is an invasive procedure, where the physician looks for abnormal tissue or growths also known as polyps.”
Rozen and colleagues initially identified five abnormal genes in a mouse model of colorectal cancer. They then further investigated these candidate biomarker genes in colon cancer tissue obtained from patients. Rozen explained that: “Not only did this show that our mouse model mimics the human disease, but more importantly, it identified genes that could be used for colorectal cancer diagnosis.” These genetic changes were also noted in otherwise normal colon cells that were not near the site of the malignancy. “This finding suggests that it may be possible to take tissue samples in more accessible regions of the GI tract or, ideally, in blood or stool, and look for biomarkers as an early indicator of disease,” continued Rozen.
The authors suggest that the discovery of these potential genetic biomarkers of colorectal cancer could enhance the diagnostic procedure by allowing individuals to be diagnosed earlier and with more accuracy, using a process that is quicker and less invasive. “This new method could help to avoid false-negative findings, which can occur in 10–15% of endoscopic procedures. The key is using the right genes. I believe the ones we have identified are good candidates,” Rozen stated.
– Written by Emily Brown
Source: McGill University press release: http://muhc.ca/newsroom/news/muhc-researchers-identify-biomarkers-could-lead-early-diagnosis-colorectal-cancer
Tenth anniversary of bevacizumab for the treatment of metastatic colorectal cancer
This year marks the tenth anniversary of the addition of the angiogenesis inhibitor, bevacizumab, to the treatment of metastatic colorectal cancer. While the drug has demonstrated efficacy, there is still controversy over its optimal treatment setting.
Multiple Phase III trials have demonstrated the efficacy of bevacizumab with a number of chemotherapy backbone regimens. However, some physicians have expressed concern over its safety profile, with documented cardiovascular adverse events, and a lack of well-documented evidence of its additional benefit to current standard chemotherapy.
Bevacizumab has demonstrated improved outcomes as a first-line therapy when combined with irinotecan/fluorouracil/levoleucovorin therapy, 5-fluorouracil/leucovorin or capecitabine. Modest improvements in progression-free survival were also observed when bevacizumab was administered in combination with FOLFOX or CAPOX.
Bevacizumab has also been investigated in the second-line setting and beyond progression in advanced colorectal cancer. In the E3200 ECOG trial, which compared FOLFOX versus FOLFOX plus bevacizumab in patients that had received irinotecan and fluoropyrimidines as first-line therapy, a 2-month improvement in median overall survival was observed. When continued beyond progression in patients who had received first-line treatments containing standard fluoropyrimidine and irinotecan or oxaliplatin-containing chemotherapy regimens plus bevacizumab, a 1.5-month improvement in overall survival was observed.
These trials demonstrate the promise of bevacizumab in the second-line setting, with either oxaliplatin or irinotecan combinations, and the benefit of continuing administration beyond progression in patients who have also received it in the first-line setting. It is still a matter of debate whether bevacizumab should be included in first-line treatment of colorectal cancer. This is due to inconclusive evidence of its increase in value when added to optimal chemotherapy backbone regimens and a lack of randomized data. Promising results from first-line combinations with EGFR inhibitors in patients with the appropriate genetic markers have contrasted with the lack of predictive markers for bevacizumab, meaning the optimal sequence between EGFR inhibitors and bevacizumab in first and second lines of treatment is yet to be elucidated. CALGB 80405, the large Phase III trial, should reveal the best treatment strategy in the first-line setting.
– Written by Caroline Telfer
Source: Salazar R, Grasseli J, Santos C, Tabernero J. Tenth anniversary of bevacizumab in colorectal cancer: has it fulfilled its promise? Future Oncol. 10(2) 149–152 (2014)
Proton therapy claims to be safest and most effective cancer treatment
Strong evidence suggests that proton therapy may be the safest and most effective way of treating many
forms of cancer. Researchers at Proton Therapy UK (London, UK), the UK branch of the Proton Therapy Center (Prague, Czech Republic), claim that proton therapy can confer significant benefit in the treatment of a wide range of cancers, including gastrointestinal tumors.
Whereas conventional radiotherapy destroys healthy tissue as it passes through the body, proton therapy is designed to precisely target the tumor site. This significantly reduces the overall side effects of treatment. The main benefits of the technique include improved protection of the lungs, preservation of patient fitness, reduced radiation risk to surrounding tissues, reduced risk of secondary tumor development and the procedure can be performed as an outpatient treatment.
Head of the Proton Therapy Center, Professor Manfred Herbst, stated that “Proton therapy is a safer form of cancer treatment than conventional radiotherapy. It is less toxic, supports better quality of life during the treatment process, and enables patients to return to a normal life immediately after it. This is a major new development in radiotherapy and we believe it will be the only way to go in the future.”
– Written by Caroline Telfer
Source: Proton therapy stakes claim as safest and most effective cancer treatment: www.imtj.com/resources/press-releases/?entryid134=432313