scholarly journals First Case of Ductal Adenocarcinoma of the Prostate with MAP3K1 Homozygous Deletion: A Case Report and Literature Review

2020 ◽  
Author(s):  
Kazunori Shojo ◽  
Takeo Kosaka ◽  
Kohei Nakamura ◽  
Hiroshi Hongo ◽  
Shuji Mikami ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Case Reports ◽  
Homozygous Deletion ◽  
Mitogen Activated Protein Kinase ◽  
Ductal Adenocarcinoma ◽  
Sequencing Data ◽  
Molecular Features ◽  
First Case ◽  
Mitogen Activated Protein ◽  
Adenocarcinoma Of The Prostate

Abstract Background: Ductal adenocarcinoma of the prostate is a rare prostate cancer variant and associated with higher stage and greater risk of recurrence and mortality. Optimal systemic therapy for metastatic ductal adenocarcinoma is not known. Many case reports are needed for further understanding of clinical and molecular features about it. Herein we report the first case of a man who was diagnosed with ductal adenocarcinoma of the prostate with mitogen-activated protein kinase 1 (MAP3K1, MEKK1) homozygous deletion.Case Presentation: A 67-year-old man presented with ductal adenocarcinoma of the prostate accompanied by multiple lung metastases and advanced bone metastases. We performed channel transurethral resection of the prostate and confirmed the diagnosis of ductal adenocarcinoma of the prostate. DNA sequencing identified a TP53 somatic point mutation (p.Gly245Ser) as the pathogenic variant. Furthermore, a homozygous deletion was observed in MAP3K1 (MEKK1). The patient received enzalutamide but deceased five months after presenting to our institution.Conclusion: To our knowledge, this is the first report of ductal adenocarcinoma of the prostate with a MAP3K1 homozygous deletion. Accumulation of whole-exome sequencing data is expected to inform future advances in therapy development.

scholarly journals First case of ductal adenocarcinoma of the prostate with MAP3K1 homozygous deletion

2021 ◽  
Author(s):  
Kazunori Shojo ◽  
Takeo Kosaka ◽  
Kohei Nakamura ◽  
Hiroshi Hongo ◽  
Hiroaki Kobayashi ◽  
...  
Keyword(s):  
Homozygous Deletion ◽  
Ductal Adenocarcinoma ◽  
First Case ◽  
Adenocarcinoma Of The Prostate

scholarly journals The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1082
Author(s):  
Amandeep Singh ◽  
Jeehoon Ham ◽  
Joseph William Po ◽  
Navin Niles ◽  
Tara Roberts ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Metastatic Potential ◽  
Pi3k Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Sequencing Data ◽  
Genetic Aberrations ◽  
Progression Model ◽  
Mitogen Activated Protein

Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.

scholarly journals MicroRNA-132 Plays an Independent Prognostic Role in Pancreatic Ductal Adenocarcinoma and Acts as a Tumor Suppressor

2019 ◽  
Vol 18 ◽  
pp. 153303381882431 ◽  
Author(s):  
Yan Chen ◽  
Huiyun Zhu ◽  
Yuqiong Wang ◽  
Yingxiao Song ◽  
Pingping Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Prognostic Factor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Mitogen Activated Protein Kinase ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Nuclear Transcription Factor ◽  
Mitogen Activated Protein

The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.

scholarly journals A Twist-Snail Axis Critical for TrkB-Induced Epithelial-Mesenchymal Transition-Like Transformation, Anoikis Resistance, and Metastasis

2009 ◽  
Vol 29 (13) ◽  
pp. 3722-3737 ◽  
Author(s):  
Marjon A. Smit ◽  
Thomas R. Geiger ◽  
Ji-Ying Song ◽  
Inna Gitelman ◽  
Daniel S. Peeper
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Lung Metastases ◽  
Cancer Prognosis ◽  
Mitogen Activated Protein Kinase ◽  
Morphological Transformation ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein ◽  
Growth Of Tumor ◽  
Kinase Pathway

ABSTRACT In a genomewide anoikis suppression screen for metastasis genes, we previously identified the neurotrophic receptor tyrosine kinase TrkB. In mouse xenografts, activated TrkB caused highly invasive and metastatic tumors. Here, we describe that TrkB also induces a strong morphological transformation, resembling epithelial-mesenchymal transition (EMT). This required TrkB kinase activity, a functional mitogen-activated protein kinase pathway, suppression of E-cadherin, and induction of Twist, a transcription factor contributing to EMT and metastasis. RNA interference (RNAi)-mediated Twist depletion blocked TrkB-induced EMT-like transformation, anoikis suppression, and growth of tumor xenografts. By searching for essential effectors of TrkB-Twist signaling, we found that Twist induces Snail, another EMT regulator associated with poor cancer prognosis. Snail depletion impaired EMT-like transformation and anoikis suppression induced by TrkB, but in contrast to Twist depletion, it failed to inhibit tumor growth. Instead, Snail RNAi specifically impaired the formation of lung metastases. Epistasis experiments suggested that Twist acts upstream from Snail. Our results demonstrate that TrkB signaling activates a Twist-Snail axis that is critically involved in EMT-like transformation, tumorigenesis, and metastasis. Moreover, our data shed more light on the epistatic relationship between Twist and Snail, two key transcriptional regulators of EMT and metastasis.

scholarly journals Successful Use of BRAF/MEK Inhibitors as a Neoadjuvant Approach in the Definitive Treatment of Papillary Craniopharyngioma

2020 ◽  
Vol 18 (12) ◽  
pp. 1590-1595
Author(s):  
Karam Khaddour ◽  
Michael R. Chicoine ◽  
Jiayi Huang ◽  
Sonika Dahiya ◽  
George Ansstas
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitor ◽  
Case Reports ◽  
Braf Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Definitive Treatment ◽  
High Morbidity ◽  
Who Grade ◽  
Suprasellar Region ◽  
Mitogen Activated Protein

Craniopharyngiomas are rare tumors that arise in the suprasellar region of the brain and are known for their aggressive nature despite their WHO grade I. This is due to the complex neuroanatomy of the sellar/suprasellar region and their proximity to the optic nerve apparatus, hypothalamic–pituitary tract, and other critical neuroanatomical structures. Definitive treatment is based on a multidisciplinary approach and often involves a combination of surgical, radiation, and medical therapy. However, there is high morbidity associated with surgery and RT due to the complex neuroanatomy of this region. Recently, BRAFV600E somatic mutation has been identified in most papillary craniopharyngiomas. This discovery has led to the novel use of RAF pathway inhibitors to treat these tumors. We report the successful use of dabrafenib (BRAF inhibitor) and trametinib (mitogen-activated protein kinase kinase inhibitor) in the neoadjuvant setting followed by definitive stereotactic radiosurgery. We propose an algorithm based on available literature on the integration of targeted therapy in the management of papillary craniopharyngiomas. Our observations, together with prior case reports, advocate the incorporation of targeted therapy for unresectable craniopharyngiomas and reinforce that treatment with dual-targeted therapy is safe and effective.

scholarly journals Autophagy as a therapeutic target in pancreatic cancer

2020 ◽  
Author(s):  
Max Piffoux ◽  
Erwan Eriau ◽  
Philippe A. Cassier
Keyword(s):  
Targeted Therapy ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Ductal Adenocarcinoma ◽  
Extracellular Signal ◽  
Anti Cancer ◽  
Mitogen Activated Protein ◽  
Cellular Components

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading to an overall poor prognosis. Despite continued research efforts, no targeted therapy has yet shown meaningful efficacy in PDAC; mutations in the oncogene KRAS and the tumour suppressor TP53, which are the most common genomic alterations in PDAC, have so far shown poor clinical actionability. Autophagy, a conserved process allowing cells to recycle altered or unused organelles and cellular components, has been shown to be upregulated in PDAC and is implicated in resistance to both cytotoxic chemotherapy and targeted therapy. Autophagy is thus regarded as a potential therapeutic target in PDAC and other cancers. Although the molecular mechanisms of autophagy activation in PDAC are only beginning to emerge, several groups have reported interesting results when combining inhibitors of the extracellular-signal-regulated kinase/mitogen-activated protein kinase pathway and inhibitors of autophagy in models of PDAC and other KRAS-driven cancers. In this article, we review the existing preclinical data regarding the role of autophagy in PDAC, as well as results of relevant clinical trials with agents that modulate autophagy in this cancer.

scholarly journals Osteonecrosis of the Jaws in Patients Receiving Anti-Angiogenic Drugs and Chemotherapeutics: Literature Review and Case Reports

2019 ◽  
Vol 46 (2) ◽  
pp. 51-56 ◽  
Author(s):  
Z. Mihaylova ◽  
R. Ugrinov ◽  
E. Aleksiev ◽  
P. Stanimirov
Keyword(s):  
Anticancer Agents ◽  
Lung Metastases ◽  
Case Reports ◽  
Osteonecrosis Of The Jaw ◽  
Surgical Removal ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
First Case ◽  
Antiresorptive Drugs ◽  
History Of

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but serious pathology associated with the use of bisphosphonates (BPs) and antiresorptive drugs in patients with bone metastases, multiple myeloma and osteoporosis. Various cases of patients with jaw bone necrosis due to BPs have recently been reported in the literature. Anti-angiogenic drugs are novel anticancer agents prescribed to patients with renal carcinoma, lung carcinoma, soft tissue metastases, etc. Anti-angiogenic drugs target the vascular endothelial growth factor’s (VEGF) signaling pathways via different mechanisms and thus inhibit tumor cell proliferation, neoangiogenesis and tumor growth. Several reports have suggested a higher incidence of MRONJ in patients treated with BPs in combination with anti-angiogenic drugs. However, there is currently no sufficient data in the literature about the risk of ONJ in patients taking anti-angiogenic drugs or cancer chemotherapy alone. We present two clinical cases of osteonecrosis of the jaw in patients treated with chemotherapy, but no history of BPs. In the first case the necrosis is related to the anti-angiogenic agent sunitinib in a patient with lung metastases and in the second case- to complex chemotherapy in a patient with acute myeloid leukemia. We recommend conservative treatment with antibiotics in both cases, together with antiseptics and surgical removal of the necrotic bone following total demarcation of the sequesters.

scholarly journals Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Francesco Baldo ◽  
Andrea Magnolato ◽  
Egidio Barbi ◽  
Irene Bruno
Keyword(s):  
Side Effects ◽  
Color Change ◽  
Standard Dose ◽  
Case Reports ◽  
Gastrointestinal Symptoms ◽  
Mitogen Activated Protein Kinase ◽  
Hair Color ◽  
Peripheral Edema ◽  
Plexiform Neurofibromas ◽  
First Case

Abstract Background Plexiform neurofibromas (PNs) are congenital tumors that affect around 50 % of the subjects with neurofibromatosis type 1. Despite being histologically benign, PNs can grow rapidly, especially in the pediatric age, and cause severe morbidities. In the past, various therapeutic approaches have been proposed to treat these masses, none of which obtained valuable results. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. The drug’s most common side effects, which usually are mild or moderate, include gastrointestinal symptoms (diarrhea, abdominal pain), dermatologic manifestations (maculo-papular and acneiform rash, paronychia, mucositis), and various laboratory test abnormalities (elevation of creatine kinase and aminotransferase). Cases presentation We report two previously undescribed adverse events in pediatric patients: peripheral edema and hair color change. The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). The edema involved the right leg, and the patient did not complain of pain. The second case of peripheral edema occurred in a 12-year-old girl after six months of therapy with selumetinib at the standard dose, involving her lower left leg. The patient initially complained of pain in that area, but it gradually and spontaneously resolved. In both patients, all the radiological exams, including lymphoscintigraphy, pelvic and abdominal ultrasound, and doppler ultrasound of the affected limb, as well as blood tests, revealed no abnormalities. Hair color change appeared in a 4-year-old boy after six months of therapy at the standard dose. The boy’s hair, whose natural color was dark blonde, became lighter in some areas. Despite the appearance of these side effects, all the patients and their families decided to continue the treatment with selumetinib, in considerations of its clinical benefits. Conclusions Since the use of selumetinib to treat plexiform neurofibromas is increasing in the pediatric population, clinicians should be aware of its side effects, so to decide whether continuing the treatment, reducing the dose or even interrupting it, when appropriate.

Head and Neck Cancer with Lung Metastases: Treatment Challenges

2019 ◽  
Vol 6 (1) ◽  
pp. 48-53
Author(s):  
Selvamalar Vengathajalam ◽  
Norhafiza Mat Lazim
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Lung Metastases ◽  
Case Reports ◽  
Primary Tumour ◽  
Treatment Options ◽  
Case Series ◽  
Low Grade ◽  
First Case

Background:Head and neck cancer has predilection of metastasising to the lung, bones or liver. The site of metastasis usually depends on the primary tumour location, the staging and the regional spread of the tumour. Patients with distant metastasis are predicted to have a poor prognosis with low survival rate. Oligometastasis is the term used for an intermediate biologic state of restricted metastatic capacity with limited number and sites of organ with metastasis. It is also defined by 5 or less than 5 metastatic lesion in a disease with a controlled primary tumour.Case Reports:In this case series, we have reported three cases of head and neck carcinomas that pose treatment dilemmas because of lung metastases. First case is a gentleman with laryngeal carcinoma with multiple small lung metastases where the treatment options of surgery versus chemoradiation was debated. The second case is a gentleman with low grade mucoepidermoid carcinoma of the parotid gland with suspicious lung spread of disease. Lastly is a patient with papillary thyroid carcinoma with florid lung metastases who completed chemoradiation.Conclusion:The presence of lung metastases does not necessarily mean that the prospect of surviving is poor for the patient. It is necessary to determine the best choice of treatment yielding the best quality of life to maximize the survival period for these patients.

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