JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Preoperative Chemotherapy in Patients With Intermediate-Risk Rectal Adenocarcinoma Selected by High-Resolution Magnetic Resonance Imaging: The GEMCAD 0801 Phase II Multicenter Trial.
Oncologist
PUBLISHED: 09-10-2014
Show Abstract
Hide Abstract
The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma.
Related JoVE Video
Pharmacogenetic predictors of outcome in patients with stage II and III colon cancer treated with oxaliplatin and fluoropyrimidine-based adjuvant chemotherapy.
Mol. Cancer Ther.
PUBLISHED: 06-30-2014
Show Abstract
Hide Abstract
Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.
Related JoVE Video
Longitudinal study of cognitive dysfunctions induced by adjuvant chemotherapy in colon cancer patients.
Support Care Cancer
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive dysfunction in patients treated with adjuvant chemotherapy for colon cancer.
Related JoVE Video
Genes associated with metabolic syndrome predict disease-free survival in stage II colorectal cancer patients. A novel link between metabolic dysregulation and colorectal cancer.
Mol Oncol
PUBLISHED: 01-16-2014
Show Abstract
Hide Abstract
Studies have recently suggested that metabolic syndrome and its components increase the risk of colorectal cancer. Both diseases are increasing in most countries, and the genetic association between them has not been fully elucidated. The objective of this study was to assess the association between genetic risk factors of metabolic syndrome or related conditions (obesity, hyperlipidaemia, diabetes mellitus type 2) and clinical outcome in stage II colorectal cancer patients. Expression levels of several genes related to metabolic syndrome and associated alterations were analysed by real-time qPCR in two equivalent but independent sets of stage II colorectal cancer patients. Using logistic regression models and cross-validation analysis with all tumour samples, we developed a metabolic syndrome-related gene expression profile to predict clinical outcome in stage II colorectal cancer patients. The results showed that a gene expression profile constituted by genes previously related to metabolic syndrome was significantly associated with clinical outcome of stage II colorectal cancer patients. This metabolic profile was able to identify patients with a low risk and high risk of relapse. Its predictive value was validated using an independent set of stage II colorectal cancer patients. The identification of a set of genes related to metabolic syndrome that predict survival in intermediate-stage colorectal cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy and avoid the toxic and unnecessary chemotherapy in patients classified as low risk. Our results also confirm the linkage between metabolic disorder and colorectal cancer and suggest the potential for cancer prevention and/or treatment by targeting these genes.
Related JoVE Video
Pancreatic biomarkers: could they be the answer?
World J. Gastroenterol.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Pancreatic ductal adenocarcinoma (PDA) is known for its poor prognosis. Most of the patients are diagnosed with advanced stages, when no curative treatment is available. Currently, despite extensive clinical research on PDA, the median overall survival remains short. Diagnosis delay and primary chemo-resistance due to its intrinsic biological nature may explain the challenges to improve our results. Our knowledge about the molecular biology of PDA has exponentially increased during the last decades and its use for the development of biomarkers could help to reach better results in the clinical setting. These biomarkers could be the clue for the improvement in PDA clinical research by earlier detection strategies with diagnostic biomarkers, and by an individualization of treatment approach with prognostic and predictive biomarkers. This review summarizes the current knowledge about the molecular biology of PDA and the status of the most important prognostic and predictive biomarkers.
Related JoVE Video
A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy.
Related JoVE Video
The return to work of cancer survivors: The experience in Spain.
Work
PUBLISHED: 09-06-2013
Show Abstract
Hide Abstract
Because of improvements in diagnosis and treatment, cancer survival has increased in recent decades. Cancer survivors may experience problems when returning to their normal lives, particularly with returning to work. In the past few decades, a number of studies examining the work-return process of cancer survivors have been conducted in a select group of countries, but comparable studies are lacking in other countries, including Spain.
Related JoVE Video
Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis.
Gut
PUBLISHED: 05-23-2013
Show Abstract
Hide Abstract
OBJECTIVE: Hypomethylation of LINE-1 elements has emerged as a distinguishing feature in human cancers. Limited evidence indicates that some LINE-1 elements encode an additional internal antisense promoter, and increased hypomethylation of this region may lead to inadvertent activation of evolutionarily methylation-silenced downstream genes. However, the significance of this fundamental epigenetic mechanism in colorectal cancer (CRC) has not been investigated previously. DESIGN: We analysed tissue specimens from 77 CRC patients with matched sets of normal colonic mucosa, primary CRC tissues (PC), and liver metastasis tissues (LM). LINE-1 methylation levels were determined by quantitative bisulfite pyrosequencing. MET, RAB3IP and CHRM3 protein expression was determined by western blotting and IHC. MET proto-oncogene transcription and 5-hydroxymethylcytosine (5-hmc) were evaluated by quantitative real-time-PCR. RESULTS: Global LINE-1 methylation levels in LM were significantly lower compared with the matched PC (PC=66.2% vs LM=63.8%; p<0.001). More importantly, we observed that specific LINE-1 sequences residing within the intronic regions of multiple proto-oncogenes, MET (p<0.001), RAB3IP (p=0.05) and CHRM3 (p=0.01), were significantly hypomethylated in LM tissues compared with corresponding matched PC. Furthermore, reduced methylation of specific LINE-1 elements within the MET gene inversely correlated with induction of MET expression in CRC metastases (R=-0.44; p<0.0001). Finally, increased 5-hmc content was associated with LINE-1 hypomethylation. CONCLUSIONS: Our results provide novel evidence that hypomethylation of specific LINE-1 elements permits inadvertent activation of methylation-silenced MET, RAB3IP and CHRM3 proto-oncogenes in CRC metastasis. Moreover, since 5-hmc content inversely correlated with LINE-1 hypomethylation in neoplastic tissues, our results provide important mechanistic insights into the fundamental processes underlying global DNA hypomethylation in human CRC.
Related JoVE Video
Molecular markers to predict outcome to antiangiogenic therapies in colorectal cancer: current evidence and future perspectives.
Cancer Treat. Rev.
PUBLISHED: 02-08-2013
Show Abstract
Hide Abstract
Angiogenesis is a universal requirement for the growth of solid tumours beyond the limits of oxygen diffusion from the existing vasculature. The expression and function of proangiogenic and antiangiogenic factors are altered in solid malignancies to drive net neoangiogenesis. Vascular endothelial growth factor (VEGF) has been confirmed in several clinical trials as an important therapeutic target in colorectal cancer (CRC) treatment. However, given that the efficacy of antiangiogenic agents appears to be limited to a subset of patients, the identification of who will obtain the greater benefit from this therapy or suffer from specific toxicities and when or for how long they should be administered in the treatment algorithm are major open questions for clinicians and challenges for present and future research. Current evidence indicates some predictive value for particular circulating measures, such as an increase in VEGF, a decrease in vascular endothelial growth factor receptor 2 (VEGFR-2) or circulating endothelial cells, tissue biomarkers, microvessel density, KRAS and BRAF gene mutations or polymorphisms affecting components of the VEGF pathway. Many questions relating to these and other surrogate biomarkers, however, remain unanswered and their clinical usefulness has yet to be proven. This review will focus on the present status of knowledge and future perspectives for developing molecular tools to foresee and monitor antiangiogenic therapy activity in CRC patients.
Related JoVE Video
Development and validation of a prognostic nomogram for terminally ill cancer patients.
J. Natl. Cancer Inst.
PUBLISHED: 10-04-2011
Show Abstract
Hide Abstract
Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease.
Related JoVE Video
Hepatocellular and biliary tract carcinomas: SEOM clinical guidelines.
Clin Transl Oncol
PUBLISHED: 08-09-2011
Show Abstract
Hide Abstract
While hepatocellular carcinoma (HCC) is a relatively common tumour with an annual incidence in the EU of 8 cases/100,000 inhabitants, bile tract carcinoma (BTC) is much less common, with an incidence of 4 cases per 100,000 inhabitants per year. In both cases, when planning treatment it is essential to perform accurate staging, evaluate hepatic functional reserve and performance status, and obtain the opinion of the patient. The only curative treatment is surgery. However, several interventional radiological techniques can help to achieve local disease control and the alleviation of symptoms. In addition, sorafenib (HCC) and chemotherapy (BTC) may contribute to prolong survival in patients with disseminated disease. Therefore, the therapeutic strategy should always be discussed and planned within a multidisciplinary tumour board.
Related JoVE Video
SEOM clinical guidelines for the treatment of anal cancer.
Clin Transl Oncol
PUBLISHED: 08-09-2011
Show Abstract
Hide Abstract
Anal carcinoma is an uncommon disorder accounting for less than 2% of large bowel malignancies and 1-6% of anorectal tumours. Its incidence ranges between 0.5 and 1% per 100,000. Local staging should be done with MR imaging using an external pelvic phased-array coil. Treatment strategy should be optimally discussed in a multidisciplinary team. HIV-positive patients seem to achieve similar response rate and overall survival to HIV-negative patients but with increased toxicity and higher local recurrences. Combined modality treatment with irradiation and chemotherapy has resulted in complete response over 90% and local control over 85%. This guide gives recommendations for diagnosis, staging and treatment.
Related JoVE Video
[Hereditary colorectal cancer].
Med Clin (Barc)
PUBLISHED: 07-11-2011
Show Abstract
Hide Abstract
Up to 5% of all diagnosed colorectal cancers has a hereditary cuase. Colon cancer arise in younger individuals, and extracolonic tumors are also frequent. A precise understanding of main syndromes will allow the proper management of these patients, including genetic counselling, screening and prophylactic surgery.
Related JoVE Video
A combined strategy of SAGE and quantitative PCR Provides a 13-gene signature that predicts preoperative chemoradiotherapy response and outcome in rectal cancer.
Clin. Cancer Res.
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
Preoperative chemoradiotherapy (CRT) is the treatment of choice for rectal cancer (RC), but half of the patients do not respond, suffer unnecessary toxicities, and surgery delays. We aimed to develop a model that could predict a clinically meaningful response to CRT by using formalin-fixed paraffin-embedded (FFPE) biopsies.
Related JoVE Video
Symptom clusters in advanced cancer.
J Pain Symptom Manage
PUBLISHED: 03-12-2011
Show Abstract
Hide Abstract
Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population.
Related JoVE Video
Gene profiling in breast cancer: time to move forward.
Cancer Treat. Rev.
PUBLISHED: 02-01-2011
Show Abstract
Hide Abstract
Gene signatures may complement clinical and pathological factors to predict prognosis and response to therapy in patients with breast cancer, and can also sub-classify these tumours into entities with different biology and treatment requirements. A number of prognostic gene signatures are commercially available at this moment and two of them have entered phase III evaluation. Specific signatures are also being assessed to predict response to a number of drug therapies. The combined use of prognostic, predictive and subtype-defining signatures will guide therapeutic decisions in the future and will facilitate development of targeted drugs in specific groups of patients. However, cost-utility issues and some technical limitations have hindered widespread adoption of gene profiling. Gene signatures will become part of the routine clinical workup only if they help making clinical decisions. The first step to achieve this will consist of the inclusion of gene signatures in the design of clinical trials with new drugs.
Related JoVE Video
Design and endpoints of clinical and translational trials in advanced colorectal cancer. a proposal from GROUP Español Multidisciplinar en Cancer Digestivo (GEMCAD).
Rev Recent Clin Trials
PUBLISHED: 01-19-2011
Show Abstract
Hide Abstract
Meta-analytic reviews of Randomized Clinical Trials (RCT) have reached contradictory conclusions regarding the benefit of medical interventions in Advanced Colorectal Cancer (ACRC). Surrogate markers of survival benefit, such as response rate (RR) and progression free-survival (PFS) often show contradictory and highly variable correlations. These contradictions can be due to differences in 1) the studies analysed (sources), 2) the quality of clinical trials (intrinsic bias in the design, biased data analysis, heterogeneous PFS definitions) and 3) the second-line strategies between arms. PFS is a more vulnerable target than overall survival (OS), but the latter can also be affected by different biases and additional medical interventions such as secondary resection of metastases or second-line therapies. Therefore the correlation between PFS and survival must be clearly stated if PFS is to be considered as a primary endpoint. Of the differences between studies, only the quality of clinical trials can be improved by a deeper knowledge of both the area of study (i.e. colorectal cancer) and the methodology needed (i.e., clinical and translational trials). The aim of this manuscript is to offer the basic resources to develop experimental trials in ACRC. To this end, techniques for diagnosis and for response assessment are discussed, prognostic factors and treatment standards are critically exposed, and notes about how to design useful translational studies are provided.
Related JoVE Video
An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer.
BMC Cancer
PUBLISHED: 06-28-2010
Show Abstract
Hide Abstract
Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.
Related JoVE Video
Palliative care is a key component of daily practice in oncology: descriptive study of hospitalisation events at an oncology treatment centre.
Support Care Cancer
PUBLISHED: 04-29-2010
Show Abstract
Hide Abstract
The impact that palliative care services have had on admission to oncology services has not been well-defined. This retrospective study was undertaken in the oncology service of a general hospital where there is also a palliative care service.
Related JoVE Video
KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis.
PLoS ONE
PUBLISHED: 09-01-2009
Show Abstract
Hide Abstract
KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.
Related JoVE Video
EPO-R expression patterns in resected gastric adenocarcinoma followed by adjuvant chemoradiation treatment.
Pathol. Oncol. Res.
PUBLISHED: 08-21-2009
Show Abstract
Hide Abstract
The primary aim was to determine whether Epo-R immunohistochemical expression is related to disease free survival (DFS) in specimens of GC from patients who underwent adjuvant chemoradiation. Specimens of gastric adenocarcinomas obtained from 44 patients who had undergone curative gastrectomy and adjuvant treatment were investigated immunohistochemically expression of Epo-R. Three patterns for Epo-R staining were defined: Pattern A (secretory cells-like staining), Pattern B (parietal-like staining) and Pattern C (chief-like staining). Median DFS was 38 months (CI 95%: 33-43) and 15 months (IC 95%: 3-27) in the pattern B and C, respectively, but it was not reached in the pattern A (p = 0.06). Our findings suggest that there may be a relationship between Epo-R expression and DFS in the patients with GC resected.
Related JoVE Video
WITHDRAWN:Bevacizumab: a safe and effective treatment in a patient with advanced colorectal cancer and repeated removal of metastases.
Anticancer Drugs
PUBLISHED: 04-09-2009
Show Abstract
Hide Abstract
withdrawn by publisher: Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorectal cancer, undergoing surgery for liver metastases and bilateral surgery for lung metastases at different time-points during her disease, is reported. Perioperative bevacizumab administration caused no complications either associated with surgery, in the early postoperative period, or in the subsequent months.
Related JoVE Video
Chemotherapy for colorectal cancer in the elderly: Whom to treat and what to use.
Cancer Treat. Rev.
PUBLISHED: 04-02-2009
Show Abstract
Hide Abstract
The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.
Related JoVE Video
Combination therapy with docetaxel and low dose of cisplatin in elderly patients with advanced non-small cell lung cancer: multicenter phase II study.
Cancer Chemother. Pharmacol.
PUBLISHED: 01-21-2009
Show Abstract
Hide Abstract
To determine the efficacy and safety of the combination therapy with docetaxel and cisplatin (CDDP) at low doses in elderly patients with advanced NSCLC.
Related JoVE Video
Thymoma and thymic carcinoma in the target therapies era.
Cancer Treat. Rev.
Show Abstract
Hide Abstract
Thymic malignancies are extremely rare although usually affect young adults and continue to remain an important health problem. Like other rare diseases, progress in thymic malignancies has been slow and the treatment cornerstone still remains surgical resection. Next generation sequencing and other advances in molecular biology are shedding light onto the multiple genetic aberrations involved and have opened a new field for research with molecularly targeted therapies such as CKIT inhibitors or anti-EGFR therapies. In this review we will summarize the current knowledge in the pathophysiology, diagnosis, prognosis and latest advances in the management of thymomas and thymic carcinomas.
Related JoVE Video
Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment?
Clin Transl Oncol
Show Abstract
Hide Abstract
Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.
Related JoVE Video
Serum interleukin-15 levels in cancer patients with cachexia.
Oncol. Rep.
Show Abstract
Hide Abstract
Interleukin-15 (IL-15) has important anabolic effects on muscle protein metabolism through a decrease in the ATP-ubiquitin-dependent proteolytic pathway. The role of IL-15 in human cancer cachexia is unknown. The aim of this study was to assess the relationship between interleukin-15 (IL-15) in cancer patients with cachexia at diagnosis of malignancy and 8 weeks later. An observational study of 21 cancer patients (with and without cachexia) and 8 healthy subjects was conducted. Body composition was measured by leg-to-leg impedance. Serum IL-15 levels were assessed at baseline and after 4 and 8 weeks. Baseline IL-15 values were similar in cancer patients and in healthy subjects. Cancer patients with lower baseline levels of IL-15 (<2 pg/ml) had significantly higher fat mass (%) along the study. Eighteen patients completed the study: five patients showed an increase of 3.7 kg at the end of the study (5.4% of body weight) and showed a mean increase of IL-15 of 1.32 pg/ml (121%) at 4 weeks and 2.32 pg/ml (197%) at 8 weeks, as compared with mean decrease of -4.1 kg (-5.3%) and -0.09 pg/ml (-2.5%) and 0.6 pg/ml (40.8%) in the 13 patients who lost weight (P=0.001 and P=0.022, respectively). Changes of IL-15 at 4 and 8 weeks were directly associated with changes in body weight, body mass index (BMI), fat-free mass and muscle mass (P<0.05), and indirectly associated with percentage of weight loss (P<0.05). In summary, although the results indicate that IL-15 does not have a role in cancer cachexia pathogenesis, the association during evolution between serum IL-15 and changes in weight and muscle mass suggests a possible role of IL-15 as a marker of the body composition response in cancer patients who are losing weight at the time of diagnosis.
Related JoVE Video
Cutaneous relapse of an ampullary carcinoma: an unusual presentation.
BMJ Case Rep
Show Abstract
Hide Abstract
This is the first ever reported case about a cutaneous relapse of small bowel adenocarcinoma. The ampulla of Vater is the area of the small bowel that presents more frequently malignant transformation, nevertheless ampullary adenocarcinomas are rare but aggressive diseases. However, distant metastases are infrequent. Cutaneous metastases constitute the 5.3% of skin tumours, and are usually found in the 12% of malignancies. Their management usually includes local treatment if they are unique and systemic treatment when they are multiple. Chemotherapy schemes used in ampullary adenocarcinoma are those used in cholangiocarcinomas, pancreas and tumours of the gallbladder; nevertheless, given the intestinal origin of these tumours combinations of capecitabine and oxaliplatin are commonly used.
Related JoVE Video
Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations.
Crit. Rev. Oncol. Hematol.
Show Abstract
Hide Abstract
The advent of the epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies (mAbs), cetuximab and panitumumab has expanded the range of treatment options for metastatic colorectal cancer (CRC). Despite these agents have paved the way to individualized therapy, our understanding why some patients respond to treatment whereas others do not remain poor. The realization that detection of positive EGFR expression by IHC does not reliably predict clinical outcome of EGFR-targeted treatment has led to an intense search for alternative predictive biomarkers. Data derived from multiple phase III trials have indicated that KRAS mutations can be considered a highly specific negative biomarker of benefit to anti-EGFR mAbs. Oncologists are now facing emerging issues in the treatment of metastatic CRC, including the identification of additional genetic determinants of primary resistance to EGFR-targeted therapy for further improving selection of patients, the explanation of rare cases of patients carrying KRAS-mutated tumours who have been reported to respond to cetuximab and panitumumab and the discovery of mechanisms of secondary resistance to EGFR-targeted therapy. Current data suggest that, together with KRAS mutations, the evaluation of EGFR gene copy number (GCN), BRAF, NRAS, PIK3CA mutations or loss of PTEN expression could also be useful for selecting patients with reduced chance to benefit from anti-EGFR mAbs. This review aims to provide an updated of the most recent data on predictive and prognostic biomarkers within the EGFR pathway, the challenges this emerging field presents and the future role of these molecular markers in CRC treatment.
Related JoVE Video
The role of capecitabine in locally advanced rectal cancer treatment: an update.
Drugs
Show Abstract
Hide Abstract
Preoperative infusional 5-fluorouracil (5-FU) and concurrent radiation therapy (RT) followed by total mesorectal surgery is the current standard of care for locally advanced rectal cancer (LAR). When compared with postoperative 5-FU-based chemoradiation, this strategy is associated with significantly lower rates of local relapse, lower toxicity and better compliance. Capecitabine is a rationally designed oral prodrug that is converted into 5-FU by intracellular thymidine phosphorylase. Substitution of infusional 5-FU with capecitabine is an attractive option that provides a more convenient administration schedule and, possibly, increased efficacy. Indeed, incorporation of capecitabine in combined modality neoadjuvant therapy for LAR has been under intense investigation during the last 10 years. Phase I and II clinical trials showed that a regimen consisting of capecitabine 825mg/m(2) twice daily for 7 days/week continuous oral administration in combination with RT is an active and well tolerated regimen, thereby being the preferred concurrent regimen. The definitive demonstration that efficacy of capecitabine/RT is similar to 5-FU/RT has been provided by the NSABP-R-04 and the German Margit trials. One approach to improve outcomes in rectal cancer is to deliver a second RT-sensitizing drug with effective systemic activity. Oxaliplatin and irinotecan are therefore good candidates. However, two phase III trials demonstrated that incorporation of oxaliplatin to capecitabine with RT did not improve early outcomes and, by contrast, increased toxicity. Capecitabine has also been combined with irinotecan. This regimen showed encouraging results in phase I and II clinical trials, which led to an ongoing phase III clinical trial. New strategies with induction chemotherapy with or without chemoradiation prior to surgery are currently under investigation. Whether or not capecitabine has a role in this setting is being investigated in ongoing trials. Incorporation of agents directed towards new targets, such as anti-epidermal growth factor receptor (EGFR) antibodies or antiangiogenic agents, in combination preoperative regimens, is being hampered by results of early trials in which efficacy outcomes with cetuximab were poor and an excessive rate of surgical complications with bevacizumab was observed. The lack of improvements in efficacy with the addition of cetuximab or bevacizumab in the adjuvant treatment of colon cancer led to concerns about further development of these agents in rectal cancer. The role of capecitabine in the postoperative adjuvant setting is the aim of the ongoing Dutch SCRIPT trial. The prediction of response associated with capecitabine has been based on expression of thymidylate synthase and dihydropyrimidine dehydrogenase, as well as on gene expression arrays. All these procedures require further validation and should be considered as investigational. In conclusion, capecitabine can safely and effectively replace intravenous continuous infusion of 5-FU in the preoperative chemoradiation setting for rectal cancer management. The addition of other new antineoplastic agents to a fluoropyrimidine-based regimen remains investigational.
Related JoVE Video
Upregulation of trefoil factor 3 (TFF3) after rectal cancer chemoradiotherapy is an adverse prognostic factor and a potential therapeutic target.
Int. J. Radiat. Oncol. Biol. Phys.
Show Abstract
Hide Abstract
Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance.
Related JoVE Video
ERCC1 and topoisomerase I expression in small cell lung cancer: prognostic and predictive implications.
Int. J. Oncol.
Show Abstract
Hide Abstract
Small cell lung cancer is the most aggressive lung cancer subtype. The standard treatment approach is based on cisplatin regimens. Although response rates to treatment are approximately 60-80%, the median survival is still very poor. Excision repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced DNA adducts and has been related with prognosis and cisplatin response. Topotecan is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and immunohistochemistry. A significant association was found between the inmunohistochemistry expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In the survival analysis, a significant correlation between a better PFS with a low TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary, our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis to predict cisplatin response and prognosis in SCLC patients.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.