Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that accounts for up to 40% of all endometrial cancer-related deaths. Recent whole-exome sequencing studies have revealed HER2/neu amplification in 27-44% of USC patients, supporting HER2 as an attractive pathway for target therapies based on monoclonal antibodies or tyrosine kinase inhibitors. Preclinical studies and a recently published prospective randomized trial with trastuzumab in combination with chemotherapy demonstrated promising results with anti-HER2-targeted therapies in advanced and recurrent USC patients. In contrast, single-agent trastuzumab or tyrosine kinase inhibitors (i.e., lapatinib) were unable to demonstrate significant clinical activity and/or durable tumor growth inhibition. Combinatorial therapies may represent novel, highly effective therapeutic strategies to overcome inborn or acquired resistance to HER2/neu-targeted therapies in HER2-amplified USC patients. This study presents a comprehensive review of the mechanisms of USC resistance to HER2-targeted therapies and potential strategies to overcome it.
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PMID:Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it. 3026 54

Nineteen topics were selected as major clinical research advances in gynecologic oncology in 2018. For cervical cancer, the importance of human papillomavirus (HPV) testing alone as primary cervical cancer screening method and negative survival impact of minimally invasive surgery in early-stage cervical cancer were addressed. For ovarian cancer, cost-effectiveness of genetic testing to prevent cancer, use of analgesics and oral pill to reduce cancer risk, efficacy of secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, update in the use of poly (ADP-ribose) polymerase inhibitor, and efficacy of anti-angiogenic targeted treatments, including bevacizumab and tyrosine kinase inhibitors, were reviewed. For corpus cancer, sentinel lymph node mapping technique, adjuvant therapy in high-risk endometrial cancer (PORTEC-3), and targeted therapy in recurrent disease were covered. For the field of radiation oncology, survival outcomes of chemoradiation compared with chemotherapy alone in metastatic cervical cancer and new findings regarding the use of neoadjuvant chemotherapy in locally advanced cervical cancer were introduced. Lastly, for breast cancer, the use of talazoparib in patients with germline BRCA1/2 mutation, ovarian suppression for premenopausal patients, adjuvant chemotherapy guided by 21-gene assay, and combination therapy of atezolizumab and nab-paclitaxel for triple-negative cancer as well as promising overall survival results of palbociclib and fulvestrant in advanced breast cancer were briefly mentioned.
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PMID:Major clinical research advances in gynecologic cancer in 2018. 3080 45

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver with high mortality and frequent recurrence. Although various therapies provide potential cure for HCC patients, unfortunately the five-year survival rate of advanced HCC remains dismal. It is critical to explore the pathogenesis of HCC and identify novel biomarkers for early HCC diagnosis. PSMD4 is a major receptor of the 26S proteasome involved in ubiquitindependent and proteasome-mediated protein degradation. In our study, PSMD4 was overexpressed in HCC tissues and cell lines determined by Northern blot, western blot and immunohistochemistry. The silencing of PSMD4 blocked cell proliferation and tumor growth, induced cell apoptosis and inhibited the proteasome activity. Western blot results showed that the knockdown of PSMD4 blocked the expression of cyclooxygenase 2 (COX2), phosphorylated Sarcoma tyrosine kinase (P-SRC) and Bcl-2, but improved the levels of p53 and Bax in HCC, lung cancer, colorectal cancer, breast cancer and endometrial cancer cell lines. Taken together, these findings indicated that the subunit of 26S proteasome PSMD4 exerts as an oncogene in HCC and other cancers via regulating the expression p53, Bcl-2 and Bax. These findings enriched the pathogenesis of HCC, and provided a new biomarker for cancers diagnosis and a new target for cancers therapy.
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PMID:Inhibition of PSMD4 blocks the tumorigenesis of hepatocellular carcinoma. 3093 Feb 24

Lenvatinib is a type I tyrosine kinase inhibitor exhibiting powerful antiangiogenic activity in cancer therapy. Displaying activity in multiple solid tumors, it has been approved in differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma as single agent or in combination. In addition, lenvatinib has shown promise in several other tumor types including medullary, anaplastic thyroid, adenoid cystic, and endometrial cancer. Exploring synergy between angiogenic and immune checkpoint inhibitors, the lenvatinib/pembrolizumab combination is poised to become the next pair of active drugs in endometrial, lung, and gastrointestinal malignancies. Despite robust activity, the drug can be difficult to tolerate. Optimization of dose and biomarkers for prediction of efficacy and toxicities will be of great help. IMPLICATIONS FOR PRACTICE: Readers will be presented with an update on U.S. Food and Drug Administration approval of lenvatinib and suggestions for off-label use in thyroid cancer and adenoid cystic carcinomas. They will become familiarized with the common side effects, frequency, and predicators of response. In addition, they will learn that different strengths of lenvatinib are prescribed and why. Finally, readers are pointed to the latest efforts to combine lenvatinib and pembrolizumab, as well as to unresolved issues such as long-term side effects/toxicities of this drug.
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PMID:Lenvatinib in Management of Solid Tumors. 3204 89

Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton's tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib's efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.
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PMID:Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review. 3253 74


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