Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials

Advani, Shailesh; Kopetz, Scott

doi:10.1002/jso.25441

Cited by 33 publications

(19 citation statements)

References 43 publications

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“…A more accurate understanding of the interaction between the immune system and tumor cells has changed therapeutic guidelines by developing new drugs. Immunotherapy with anti-PD-1 mAbs (monoclonal antibodies) pembrolizumab and nivolumab, and anti-CTLA-4 mAbs like ipilimumab have shown promising results in metastatic CRC [8] and are US Food and Drug Administration (FDA) approved for microsatellite instability-high (MSI-H) CRC [9]. The combination of nivolumab CAR T-cell therapy manipulates the immune system by collecting and using immune cells to treat cancer.…”

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Sur

Havași

Căinap

et al. 2020

JCM

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Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Sur

Havași

Căinap

et al. 2020

JCM

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“… 3 Once tumors become resistant to standard first- and second-line therapy, including appropriate biologic epidermal growth factor receptor antibody or vascular endothelial growth factor receptor antibody therapy, there are few options that render a robust response in microsatellite stable cancers. 4 To this end, there is a critical gap for novel therapy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer

Phan

Nguyen

Salazar

et al. 2020

Molecular Therapy - Oncolytics

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Baicalein is a Chinese herbal compound extracted from Scutellaria baicalensis that has anti-tumor properties. The aim of this study was to elucidate the mechanisms of action of baicalein against human colorectal cancer cell lines and to assess whether the anti-proliferative effects of baicalein may be amplified with autophagy inhibition. Human colon cancer cell lines (HT-29, HCT-116, SW480, and SW620) were treated with baicalein alone and in combination with the autophagy inhibitor chloroquine (CQ). Baicalein reduced cell viability in all four colon cancer lines in a dose-dependent fashion. Combination treatment of baicalein and the autophagy inhibitor CQ significantly decreased cell viability compared with baicalein alone in HT-29 and HCT-116 cell lines. Western blot analysis of the HCT-116 cell line treated with both baicalein and CQ demonstrated increased expression of LC3-II, a component of autophagy. The combination of baicalein with CQ culminated in activation of caspase-3-mediated apoptosis. These findings demonstrate that inhibition of autophagy enhanced apoptotic cell death induced by baicalein treatment in colon cancer cell lines. Future work will assess other targetable apoptotic pathways activated by baicalein and autophagy inhibition.

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“…Human colorectal cancer (CRC) is the second leading cause of cancer death in the US, and~25% of patients with CRC are incurable at the time of diagnosis [1,2]. Genetic heterogeneity is inherent to this disease, providing tumor cells with the ability to rapidly adapt and resist treatments [3,4].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas

Preston

Stiffler

2020

BMC Cancer

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Background: The loss of a single copy of adenomatous polyposis coli (Apc) in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)-expressing colonic progenitor cells induces rapid growth of adenomas in mice with high penetrance and multiplicity. The tumors lack functional APC, and a genetic loss of heterozygosity of Apc was previously observed. Methods: To identify genomic features of early tumorigenesis, and to profile intertumoral genetic heterogeneity, tumor exome DNA (n = 9 tumors) and mRNA (n = 5 tumors) sequences were compared with matched nontumoral colon tissue. Putative somatic mutations were called after stringent variant filtering. Somatic signatures of mutational processes were determined and splicing patterns were observed. Results: The adenomas were found to be genetically heterogeneous and unexpectedly hypermutated, displaying a strong bias toward G:C > A:T mutations. A genetic loss of heterozygosity of Apc was not observed, however, an epigenetic loss of heterozygosity was apparent in the tumor transcriptomes. Complex splicing patterns characterized by a loss of intron retention were observed uniformly across tumors. Conclusion: This study demonstrates that early tumors originating from intestinal stem cells with reduced Lrig1 and Apc expression are highly mutated and genetically heterogeneous, with an inflammation-associated mutational signature and complex splicing patterns that are uniform across tumors.

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Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials

Cited by 33 publications

References 43 publications

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer

Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas

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