Current and future colorectal cancer screening strategies.
Ontology highlight
ABSTRACT:
SUBMITTER: Shaukat A
PROVIDER: S-EPMC9063618 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite the recent advances in the systemic treatment of metastatic colorectal cancer (mCRC), prognostic outcomes have remained to be poor. Thus, what is needed is an innovative treatment approach. Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) have exhibited a durable response and dominated the treatment of various tumor types. However, in mCRC, the clinical benefit is limited in patients with deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H), comprising approximately 5% of mCRC cases, and some do not respond to ICI treatment. Thus, further research is needed to identify predictive biomarkers. The most urgent need is developing effective immunotherapy for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) cancer, which comprises 95% of mCRC cases. Tumors with the pMMR/MSS phenotype often exhibit a lower tumor mutation burden and fewer tumor-infiltrating lymphocytes than dMMR/MSI-H, leading to immune tolerance and evasion in the tumor microenvironment. Therefore, a number of investigative studies aimed at overcoming tumor resistance in current immunotherapy approaches are underway. A better understanding on the complexity and diversity of the immune system's functioning within the tumor microenvironment will increase the potential for developing predictive biomarkers and novel therapeutic strategies to potentiate anti-tumor immunity in patients with mCRC. In this review, we summarize the most recent advances in immunotherapy based on the findings of pivotal clinical trials for patients with mCRC, highlighting potent therapeutic approaches and predictive biomarkers.
| S-EPMC7843143 | biostudies-literature
Project description:Even though significant improvements in the treatment of colorectal cancer (CRC) have been made in recent years, survival rates for metastatic colorectal cancer (mCRC) are poor. Effective treatment options for metastatic colorectal cancer remain limited, and new therapeutic strategies are desperately needed. Several tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) that target angiogenesis, a critical process for facilitating tumor cell growth, invasion, and metastasis, are either approved or in clinical development for the treatment of mCRC. Many of these agents have shown efficacy in mCRC, both as single agents and in combination with standard chemotherapy regimens. However, there is a need for predictive markers of response to identify those patients most likely to benefit from antiangiogenic therapy, and, to date, no markers of this type have been validated in patients. Additionally, because antiangiogenic agents typically cause cytostatic as opposed to cytotoxic antitumor effects, it is important to determine the best strategies for evaluating therapeutic response in mCRC to ensure maximum clinical benefit. In this review, we summarize the efficacy and tolerability of approved and investigational antiangiogenic agents for the treatment of mCRC. We also discuss potential markers of response to antiangiogenic agents and how these markers, along with appropriate endpoint selection, can improve clinical trial design.
| S-EPMC5298403 | biostudies-literature
Project description:The vasculature is a key player and regulatory component in the multicellular microenvironment of solid tumors and, consequently, a therapeutic target. In colorectal carcinoma (CRC), antiangiogenic treatment was approved almost 20 years ago, but there are still no valid predictors of response. In addition, treatment resistance has become a problem. Vascular heterogeneity and plasticity due to species-, organ-, and milieu-dependent phenotypic and functional differences of blood vascular cells reduced the hope of being able to apply a standard approach of antiangiogenic therapy to all patients. In addition, the pathological vasculature in CRC is characterized by heterogeneous perfusion, impaired barrier function, immunosuppressive endothelial cell anergy, and metabolic competition-induced microenvironmental stress. Only recently, angiocrine proteins have been identified that are specifically released from vascular cells and can regulate tumor initiation and progression in an autocrine and paracrine manner. In this review, we summarize the history and current strategies for applying antiangiogenic treatment and discuss the associated challenges and opportunities, including normalizing the tumor vasculature, modulating milieu-dependent vascular heterogeneity, and targeting functions of angiocrine proteins. These new strategies could open perspectives for future vascular-targeted and patient-tailored therapy selection in CRC.
| S-EPMC10930912 | biostudies-literature
Project description:The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally aims to induce cell death. However, apoptosis resistance is the major cause for insufficient therapeutic success and disease relapse in gastrointestinal oncology. Various compounds have been developed and evaluated with the aim to meet with this obstacle by triggering cell death in cancer cells. The aim of this review is to illustrate current approaches and future directions in targeting cell death signaling in colorectal cancer. The complex signaling network of apoptosis will be demonstrated and the "druggability" of targets will be identified. In detail, proteins regulating mitochondrial cell death in colorectal cancer, such as Bcl-2 and survivin, will be discussed with respect to potential therapeutic exploitation. Death receptor signaling and targeting in colorectal cancer will be outlined. Encouraging clinical trials including cell death based targeted therapies for colorectal cancer are under way and will be demonstrated. Our conceptual understanding of cell death in cancer is rapidly emerging and new types of controlled cellular death have been identified. To meet this progress in cell death research, the implication of autophagy and necroptosis for colorectal carcinogenesis and therapeutic approaches will also be depicted. The main focus of this topic highlight will be on the revelation of the complex cell death concepts in colorectal cancer and the bridging from basic research to clinical use.
| S-EPMC3934462 | biostudies-literature
Project description:Colorectal cancer (CRC) screening has been supported by strong research evidence and recommended in clinical practice guidelines for more than a decade. Yet screening rates in the United States remain low, especially relative to other preventable diseases such as breast and cervical cancer. To understand the reasons, the National Cancer Institute and Agency for Healthcare Research and Quality sponsored a review of CRC screening implementation in primary care and a program of research funded by these organizations. The evidence base for improving CRC screening supports the value of a New Model of Primary Care Delivery: 1. a team approach, in which responsibility for screening tasks is shared among other members of the practice, would help address physicians' lack of time for preventive care; 2. information systems can identify eligible patients and remind them when screening is due; 3. involving patients in decisions about their own care may enhance screening participation; 4. monitoring practice performance, supported by information systems, can help target patients at increased risk because of family history or social disadvantage; 5. reimbursement for services outside the traditional provider-patient encounter, such as telephone and e-mail contacts, may foster enhanced screening delivery; 6. training opportunities in communication, cultural competence, and use of information technologies would improve provider competence in core elements of screening programs. Improvement in CRC screening rates largely depends on the efforts of primary care practices to implement effective systems and procedures for screening delivery. Active engagement and support of practices are essential for the enormous potential of CRC screening to be realized.
| S-EPMC2305744 | biostudies-other
Project description:BackgroundIn 2014, a national campaign was launched to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018; it is unknown whether there is sufficient colonoscopy capacity to reach this goal. This study estimated the number of colonoscopies needed to screen 80% of the eligible population with fecal immunochemical testing (FIT) or colonoscopy and determined whether there was sufficient colonoscopy capacity to meet the need.MethodsThe Microsimulation Screening Analysis-Colon model was used to simulate CRC screening test use in the United States (2014-2040); the implementation of a national screening program in 2014 with FIT or colonoscopy with 80% participation was assumed. The 2012 Survey of Endoscopic Capacity (SECAP) estimated the number of colonoscopies that were performed and the number that could be performed.ResultsIf a national screening program started in 2014, by 2024, approximately 47 million FIT procedures and 5.1 million colonoscopies would be needed annually to screen the eligible population with a program using FIT as the primary screening test; approximately 11 to 13 million colonoscopies would be needed annually to screen the eligible population with a colonoscopy-only screening program. According to the SECAP survey, an estimated 15 million colonoscopies were performed in 2012, and an additional 10.5 million colonoscopies could be performed.ConclusionsThe estimated colonoscopy capacity is sufficient to screen 80% of the eligible US population with FIT, colonoscopy, or a mix of tests. Future analyses should take into account the geographic distribution of colonoscopy capacity. Cancer 2016;122:2479-86. © 2016 American Cancer Society.
| S-EPMC5559728 | biostudies-literature
Project description:Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66-90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed.
| S-EPMC4209818 | biostudies-other
Project description:Purpose of Review:The breast tumor microenvironment is immunosuppressive and is increasingly recognized to play a significant role in tumorigenesis. A deeper understanding of normal and aberrant interactions between malignant and immune cells has allowed researchers to harness the immune system with novel immunotherapy strategies, many of which have shown promise in breast cancer. This review discusses the application of immunotherapy to the treatment of breast cancer. Recent Findings:Both basic science and clinical trial data are rapidly developing in the use of immunotherapy for breast cancer. The current clinical trial landscape includes therapeutic vaccines, immune checkpoint blockade, antibodies, cytokines, and adoptive cell therapy. Summary:Despite early failures, the application of immunotherapeutic strategies to the treatment of breast cancer holds promise.
| S-EPMC5894864 | biostudies-literature
Project description:BackgroundAlthough uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be.MethodsThe MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years).ResultsWith current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation.ConclusionsCurrently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.
| S-EPMC6988584 | biostudies-literature
Project description:BRAF mutations constitute an important poor prognostic factor in metastatic colorectal cancer (mCRC) and the development of treatments in this context is of great necessity to prolong patient survival. Although the association between BRAF mutations and microsatellite instability (MSI) has been known for several years, previous clinical trials have revealed that the former has a limited prognostic impact and that immune checkpoint inhibitors offer a significant survival benefit to mCRC patients with both characteristics. Furthermore, the genomic classification of BRAF mutations according to their molecular functions enables greater understanding of the characteristics of mCRC patients with BRAF mutations, with therapeutic strategies based on this classification made more ideal to improve poor prognosis through the delivery of targeted therapies. Recently, a phase III trial was conducted in previously treated mCRC patients with BRAF V600E-mutated tumors and revealed that the combination therapy approach of BRAF inhibition and anti-epidermal growth factor receptor antibody therapy with or without MEK inhibition was more efficacious than standard chemotherapy alone. This review discusses current treatment strategies and future perspectives in BRAF-mutated mCRC.
| S-EPMC8027060 | biostudies-literature