Systemic treatment for metastatic colorectal cancer in the era of precision medicine

Sandhu, Jaideep; Lavingia, Viraj; Fakih, Marwan

doi:10.1002/jso.25421

Cited by 62 publications

(57 citation statements)

References 132 publications

(260 reference statements)

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“…Those mutations can appear in oncogenes, tumor suppressor genes and genes related to DNA repair mechanisms [3]. Current treatment for CRC involves a variety of approaches, including surgery and radiotherapy, as well as the use of chemotherapeutic drugs such as FOLFOX and FOLFIRI [4][5][6]. Additionally, monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR) combined with traditional chemotherapy have been applied to improve the outcome of CRC [7].…”

Section: Introductionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.

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Section: Introductionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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“…The monoclonal antibodies (mAbs) cetuximab and panitumumab are among the most common targeted therapies used in late-stage CRC. However, they are only effective in a small percentage of patients [11][12][13] due to either intrinsic or acquired resistance to this type of therapy. Unfortunately, even the patients that initially respond to EGFR antagonists usually acquired resistance over time [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

et al. 2020

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Global statistics have placed colorectal cancer (CRC) as the third most frequently diagnosed cancer and the fourth principal cause of cancer-related deaths worldwide. Improving survival for CRC is as important as early detection. Personalized medicine is important in maximizing an individual’s treatment success and minimizing the risk of adverse reactions. Approaches in achieving personalized therapy in CRC have included analyses of specific genes with its clinical implications. Tumour genotyping via next-generation sequencing has become a standard practice to guide clinicians into predicting tumor behaviour, disease prognosis, and treatment response. Nevertheless, better prognostic markers are necessary to further stratify patients for personalized treatment plans. The discovery of new markers remains indispensable in providing the most effective chemotherapy in order to improve the outcomes of treatment and survival in CRC patients. This review aims to compile and discuss newly discovered, less frequently mutated genes in CRC. We also discuss how these mutations are being used to assist therapeutic decisions and their potential prospective clinical utilities. In addition, we will summarize the importance of profiling the large genomic rearrangements, gene amplification, and large deletions and how these alterations may assist in determining the best treatment option for CRC patients.

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“…Over the past decades, adults affected by CRC have showed significant improvement in overall survival. This is in part due to the better understanding of the tumor's molecular biology and the consequent use of molecular targets, and to more aggressive surgical approaches [3,4].…”

Section: Introductionmentioning

confidence: 99%

Targeting Epidermal Growth Factor Receptor (EGFR) in Pediatric Colorectal Cancer

Pasquale

Crocoli

Caldaro

et al. 2020

Cancers

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Background: Colorectal carcinoma (CRC) is very rare in the pediatric and adolescent age range and clinical management is performed according to adult protocols. We report, for the first time in the literature, a case of a child with metastatic CRC successfully treated with panitumumab associated to chemotherapy. Methods: A twelve-year-old male was diagnosed with CRC with nodal metastasis and peritoneal neoplastic effusion. After performing a genetic evaluation, in light of the absence of mutations in RAS family genes, anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody, panitumumab, was added to chemotherapy FOLFOXIRI. Results: The child successfully responded to therapy with normalization of the Carbohydrate Antigen (CA) 19.9 value after the third cycle of treatment. After the sixth cycle, he underwent surgery that consisted in sigmoid resection with complete D3 lymphadenectomy. At histological evaluation, no residual neoplastic cells were detectable in the surgical specimen. He completed 12 cycles of chemotherapy plus panitumomab and he is alive without disease 14 months from diagnosis. Conclusions: Our results suggest performing mutational screening for colorectal cancer also in the pediatric setting, in order to orient treatment that should include targeted therapies.

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Systemic treatment for metastatic colorectal cancer in the era of precision medicine

Cited by 62 publications

References 132 publications

HSPA4 knockdown retarded progression and development of colorectal cancer

HSPA4 knockdown retarded progression and development of colorectal cancer

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

Targeting Epidermal Growth Factor Receptor (EGFR) in Pediatric Colorectal Cancer

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