Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

AbstractPurpose of ReviewTreatment options for patients with metastatic colorectal cancer continue to advance as the therapeutic implications of the molecular subtypes of this disease are becoming better understood. DNA sequencing and mismatch repair assessment are now standard of care analyses for patients with metastatic colorectal cancer This review describes important aspects of the biology of the clinically relevant molecular subtypes of colorectal cancer based on the current standard of care testing. In addition, the clinical treatment strategies available now and potentially in the future for these colorectal cancer subtypes are discussed.Recent FindingsCurrently, for metastatic colorectal cancer, standard of care molecular testing is done for mutations in exons 2, 3, and 4 ofKRAS andNRAS, andBRAF V600E. Testing for mismatch repair (MMR) deficiency/microsatellite instability (MSI) status is also done. These aberrations are well known to change the clinical prognosis and guide patients ’ treatment strategies. Additionally, three new subtypes have emerged:PIK3CAmut,HER2 amplified, andNTRK fusions. With the addition of these emerging subtypes, tumor heterogeneity further validates the need to examine mCRC as a heterogeneous disease. Here, we present recent exciting data from translational research and clinical trials exhibiting possible distinct treatment strategies for these different subtypes.SummaryAltogether, these data show promising treatment strategies for ma...
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research

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ConclusionsThe combination of niraparib and irinotecan/SN38 is effective in an in vitro model of CRC. MAPK activation, MSI and mutation in HRR-associated genes are predictors of synergism and are currently being validated in in vivo and ex vivo models. These findings could lead to a better patient selection for this combination in CRC.Legal entity responsible for the studyThe authors.FundingUniversit à della Campania Luigi Vanvitelli; Associazione Italiana per la Ricerca sul Cancro (AIRC).DisclosureP.P. Vitiello: Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Research grant/Funding (inst...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use. We investigated whether CRC can be stratified routinely within a small district general hospital to inform clinical decision making at local multidisciplinary team meeting/tumor board level. We evaluated mismatch repair (MMR) and EGFR signaling pathways using predominantly in-house immunohistochemical (IHC) tests (MSH2, MSH6, MLH1, PMS2, BRAF-...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Online Articles: Research Article Source Type: research
Conclusions In the new era of targeted therapy, treatment options are increasingly based on the precise molecular and genetic profiling of tumor cells (58). Currently, the main challenge for further novel drug development in targeted therapy is the clarification of specific molecular mechanisms underlying the varied forms of tumors in clinic. It has been acknowledged that cancer is caused by a set of driver mutations. In this regard, it is of great significance to: (1) identify and validate key mutant genes and proteins in cancers as new targets; (2) identify patients most likely and unlikely to benefit from certain targe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 19 October 2018Source: European Journal of Surgical OncologyAuthor(s): Yang Feng, Yaqi Li, Sanjun Cai, Junjie PengAbstractBackgroundHER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy.MethodsWe analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II c...
Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-EGFR and anti-VEGF agents, the relevance of primary tumour location and novel subgroups such as BRAF mutated, HER2 amplified and mismatch-repair deficient cancers. Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for mCRC. The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumo...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Opinion statementChoosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient ’s performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) o...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide but associated mortality has declined in recent decades. Genomic profiling of the disease has resulted in the definition of subsets of patients-for example, KRAS, NRAS, or BRAF mutated; Her2 amplified; and mismatch repair deficient-which has enabled personalization of therapeutic decision making. These subsets are guiding drug development and combination therapy approaches using both targeted therapies and immunotherapies. Further refinement based on molecular discoveries and the emergence of newer technologies to enable new dis...
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: Surg Oncol Clin N Am Source Type: research
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide but associated mortality has declined in recent decades. Genomic profiling of the disease has resulted in the definition of subsets of patients —for example, KRAS, NRAS, or BRAF mutated; Her2 amplified; and mismatch repair deficient—which has enabled personalization of therapeutic decision making. These subsets are guiding drug development and combination therapy approaches using both targeted therapies and immunotherapies. Further refi nement based on molecular discoveries and the emergence of newer technologies to enable new discove...
Source: Surgical Oncology Clinics of North America - Category: Surgery Authors: Source Type: research
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