Systemic Therapy in BRAF V600E-Mutant Metastatic Colorectal Cancer: Recent Advances and Future Strategies

AbstractPurpose of ReviewThis review seeks to detail the clinical and pathologic features specific toBRAFV600E colorectal cancer. Application of novel preclinical findings translated into the clinic for the development of new therapeutic options for patients withBRAFV600E metastatic colorectal cancer will be detailed.Recent FindingsWhile BRAF inhibitors as monotherapy do not have the same clinical activity for colorectal cancer relative to other solid tumors harboring an oncogenicBRAFV600E mutation, combination approaches targeting BRAF + MEK + EGFR hold promise for patients withBRAFV600E colorectal cancer.SummarySimultaneous targeting of multiple drivers along the MAPK pathway improves clinical outcomes for patients withBRAFV600E colorectal cancer. Targeted therapies and immunotherapy hold great promise in the years to come for patients with this subtype of colorectal cancer.
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research

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ConclusionsThe present case supports the efficacy of immune checkpoint inhibition in mCRC with heterogeneity in MMR/microsatellite instability status. Clinical issues that may arise in these rare patients are discussed in detail.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and β chain (TRB) genes. Full-lengthTRA andTRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven uniqueTRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-tran...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
i H Abstract Cancer immunotherapy with immune checkpoint inhibitors (ICIs) such as programmed death ligand-1 (PD-L1) blockers offers pronounced clinical benefit with durable responses and a manageable safety profile. Patients with a high risk of immune-related adverse events are generally excluded from clinical trials testing ICI therapy. Thus, only a little information on the safety and clinical outcome of patients treated with an ICI after allogeneic haematopoietic cell transplantation (HCT) is currently available. Here, we report the characteristics and outcomes of six patients with, respectively, clear cell re...
Source: Swiss Medical Weekly - Category: General Medicine Authors: Tags: Swiss Med Wkly Source Type: research
This article will provide a practical concise overview of the current landscape of immunotherapy in CRC for the practicing oncologist along with a representative case presentation from our community oncology practice. PMID: 31661153 [PubMed - in process]
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
We present here a DL based method to enumerate and quantify the immune infiltration in colorectal and breast cancer bulk RNA-Seq samples starting from scRNA-Seq. Our method makes use of a Deep Neural Network (DNN) model that allows quantification not only of lymphocytes as a general population but also of specific CD8+, CD4Tmem, CD4Th and CD4Tregs subpopulations, as well as B-cells and Stromal content. Moreover, the signatures are built from scRNA-Seq data from the tumor, preserving the specific characteristics of the tumor microenvironment as opposite to other approaches in which cells were isolated from blood. Our method...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
CONCLUSIONS: Collectively, these data demonstrate that the synergistic combination of entinostat, N-803, and vaccine elicits potent anti-tumor activity by generating a more inflamed TME. These findings thus form the rationale for the use of this combination of agents for patients harboring poorly or non-inflamed solid carcinomas. PMID: 31645354 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractDiffusing alpha-emitters radiation therapy (DaRT) is the only known method for treating solid tumors with highly destructive alpha radiation. More importantly, as a monotherapy, DaRT has been shown to induce a systemic antitumor immune response following tumor ablation. Here, immunomodulatory strategies to boost the antitumor immune response induced by DaRT, and the response specificity, were investigated in the colon cancer CT26 mouse model. Local treatment prior to DaRT,  with the TLR3 agonist poly I:C, was sufficient to inhibit tumor growth relative to poly I:C or DaRT alone. DaRT used in combination with t...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Conclusion: Our findings identify PTC-209 as a promising anticancer agent for the treatment of solid tumors either alone and/or in combination with the standard cytotoxic drugs cisplatin and camptothecin and the natural product Frondoside-A.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Creatine, the organic acid that is popularly taken as a supplement by athletes and bodybuilders, serves as a molecular battery for immune cells by storing and distributing energy to power their fight against cancer, according to new UCLA research.The study, conducted in mice and published in the Journal of Experimental Medicine, is the first to show that creatine uptake is critical to the anti-tumor activities of CD8 T cells, also known as killer T cells, the foot soldiers of the immune system. The researchers also found that creatine supplementation can improve the efficacy of existing immunotherapies.“Because oral ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
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