Molecular profiling in gastroesophageal cancer —clinical routine and future perspective

SummaryAlthough several large clinical trials have been conducted in order to investigate targeted inhibition of several molecular pathways in gastric cancer, only a  limited number of targeted therapies have been introduced in clinical routine. Besides scientific interest, international guidelines recommend investigation of some distinct molecular alterations, which are associated with therapeutic consequences. These are (i) human epidermal growth factor rece ptor 2 (HER2), (ii) programmed death receptor 1 (PD-L1) and (iii) microsatellite instability (MSI). There are some emerging markers, such as Epstein–Barr virus (EBV), which might also be associated with a favorable response to immunotherapy. These routine and potential markers will be further d iscussed in the scope of this short review.
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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AbstractThe discovery of human epidermal growth factor receptor 2 (HER2) overexpression in 15 –20% of gastric adenocarcinomas has been a key advance in the global care of this disease. Validated by the ToGA trial in the first-line setting of advanced HER2-positive (+) gastric cancer (GC), trastuzumab, an anti-HER2 monoclonal antibody (mAb), was the first therapeutic agent to significantly improve the prognosis of these patients. Since these results, many attempts have been made to improve the clinical outcomes of patients with HER2+ GC. However, all the other HER2-targeting molecules have failed to show a survival be...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
Conclusions: For patients with HER2-positive advanced gastric cancer who have developed resistance to trastuzumab, pyrotinib is a promising new agent, which can be used as salvage therapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsGC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
Abstract Efficacy data from the KATHERINE clinical trial comparing ado-trastuzumab emtansine (T-DM1) to trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer with residual disease after neoadjuvant therapy (hazard ratio for invasive disease or death, 0.50; P
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsIn this study, M+P demonstrated tolerability and preliminary evidence of anti-tumor activity as a chemotherapy-free regimen in 2nd line HER2+ GC; biomarker analysis suggests an association with higher expression and retention of HER2 and PD-L1 together with pre-existing anti-HER2 immunity.Clinical trial identificationNCT02689284.Legal entity responsible for the studyMacroGenics, Inc.FundingMacroGenics, Inc.DisclosureH. Park: Research grant / Funding (institution): Ambrx; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution):...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the ren...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H2Mab-41 (IgG2b, kappa), and the antitumor activity of H2Mab-41 was investigated using mouse xenograft models. Caco-2 cells (human colon cancer cell line), which expresses HER2, were subcutaneously implanted into the flanks of nude mice. H2Mab-41 and control mouse IgG were injected three times into the peritoneal cavity of mice. H2Mab-41 significantly reduced tumor development of Caco-2 xenograft in comparison with the control mouse IgG on days 5, 8, 11, 15, and 19. Taken together, these results suggest that H2Mab-41 is useful for antibody therapy aga...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsBased on recent and ongoing studies, eligible patients who have progressed beyond the first-line cytotoxic chemotherapy may benefit from immunotherapy. This review outlines the checkpoint inhibitors that are currently or previously being investigated for patients with metastatic UGI cancers.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
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