Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinomas (HCC) are the most common primary hepatic neoplasm of dogs and occur at a high prevalence in captive fennec foxes ( Vulpes zerda). Of 54 captive fennec fox submissions to Northwest ZooPath, 15 (28%) foxes were diagnosed with HCC. This group consisted of nine males, four females, and two foxes of unspecified gender. Affected foxes ranged in age from 8 to 13 yr (mean 10.3 yr). Clinical signs included weight loss/inappetence ( n = 2), lethargy/weakness/ataxia ( n = 3), and seizures-shaking/tremors ( n = 4). Hematologic abnormalities included elevated liver enzymes ( n = 5), hypoglycemia ( n = 3), anemia ( n = 2), and elevated renal analytes ( n = 2). In eight cases, a palpable or visible hepatic mass was identified. The gross morphologic patterns had been recorded or photodocumented for 13 HCC; these were reclassified according to the human World Health Organization (WHO) classification of hepatic neoplasms as massive ( n = 8), nodular ( n = 4), and diffuse ( n = 1). The histomorphologic pattern according to the WHO classification of hepatic neoplasms was determined for all 15 HCC with the majority of HCC ( n = 12) being classified as mixed and two HCC as trabecular and one as compact. Trabecular ( n = 11), pseudoacinar ( n = 7), compact ( n = 6), and scirrhous ( n = 1) patterns were observed in the 12 mixed HCC. All HCC were well-differentiated, but seven cases had moderate anisokaryosis. In seven HCC, a significant portion of neoplastic cells were identified as clear cells and six cases had a pelioid pattern. Necrosis was detected in six HCC, affecting between 5-40% of the neoplastic cells. As no metastases were noted at time of diagnosis, based on morphologic similarities to canine HCC, complete surgical removal of the affected liver lobe is suspected to be associated with a favorable prognosis.
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PMID:HEPATOCELLULAR NEOPLASMS IN CAPTIVE FENNEC FOXES ( VULPES ZERDA). 3059 39

TRK fusions are oncogenic drivers of various adult and paediatric cancers. The first-generation TRK inhibitors, larotrectinib and entrectinib, were granted landmark, tumour-agnostic regulatory approvals for the treatment of these cancers in 2018 and 2019, respectively. Brisk and durable responses are achieved with these drugs in patients, including those with locally advanced or metastatic disease. In addition, intracranial activity has been observed with both agents in TRK fusion-positive solid tumours with brain metastases and primary brain tumours. While resistance to first-generation TRK inhibition can eventually occur, next-generation agents such as selitrectinib (BAY 2731954, LOXO-195) and repotrectinib were designed to address on-target resistance, which is mediated by emergent kinase domain mutations, such as those that result in substitutions at solvent front or gatekeeper residues. These next-generation drugs are currently available in the clinic and proof-of-concept responses have been reported. This underscores the utility of sequential TRK inhibitor use in select patients, a paradigm that parallels the use of targeted therapies in other oncogenic driver-positive cancers, such as ALK fusion-positive lung cancers. While TRK inhibitors have a favourable overall safety profile, select on-target adverse events, including weight gain, dizziness/ataxia and paraesthesias, are occasionally observed and should be monitored in the clinic. These side-effects are likely consequences of the inhibition of the TRK pathway that is involved in the development and maintenance of the nervous system.
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PMID:TRK inhibitors in TRK fusion-positive cancers. 3173 26

The development of brain and central nervous system (CNS) metastases from primary gynecologic cancers is an extremely uncommon but deadly process. Through this retrospective case series of patients treated at a single institution from 2004 to 2018, we aim to explore potential clinical patterns of this phenomenon with respect to primary tumor type, histology, and symptomatology. A total of 42 patients were identified with CNS metastases, with 24 patients having endometrial cancer, 9 patients with ovarian cancer, 5 patients with cervical cancer, and 4 patients with gestational trophoblastic neoplasia (GTN). The two most common presenting complaints were headache and ataxia. Most patients (67%) presented with more than one lesion on imaging and the frontal lobe was most likely to be involved. The median age of diagnosis for both primary cancer and CNS metastasis were significantly younger in the GTN group when compared to other cancers. Meningeal involvement was more prevalent in patients with cervical cancer. Over 83% of endometrial cancer patients in this cohort had type II histologies, a significantly higher percentage than that in the general population. While the rarity of CNS metastases in primary gynecologic malignancies precludes routine screening, patients diagnosed with more aggressive histologic subtypes of endometrial and uterine cancers may benefit from a lowered threshold of brain imaging in the context of new onset neurological symptoms.
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PMID:Clinical characteristics of CNS metastases from primary gynecologic cancers. 3186 33

TRK fusions are oncogenic drivers of various adult and paediatric cancers. The first-generation TRK inhibitors, larotrectinib and entrectinib, were granted landmark, tumour-agnostic regulatory approvals for the treatment of these cancers in 2018 and 2019, respectively. Brisk and durable responses are achieved with these drugs in patients, including those with locally advanced or metastatic disease. In addition, intracranial activity has been observed with both agents in TRK fusion-positive solid tumours with brain metastases and primary brain tumours. While resistance to first-generation TRK inhibition can eventually occur, next-generation agents such as selitrectinib (BAY 2731954, LOXO-195) and repotrectinib were designed to address on-target resistance, which is mediated by emergent kinase domain mutations, such as those that result in substitutions at solvent front or gatekeeper residues. These next-generation drugs are currently available in the clinic and proof-of-concept responses have been reported. This underscores the utility of sequential TRK inhibitor use in select patients, a paradigm that parallels the use of targeted therapies in other oncogenic driver-positive cancers, such as ALK fusion-positive lung cancers. While TRK inhibitors have a favourable overall safety profile, select on-target adverse events, including weight gain, dizziness/ataxia and paraesthesias, are occasionally observed and should be monitored in the clinic. These side-effects are likely consequences of the inhibition of the TRK pathway that is involved in the development and maintenance of the nervous system.
 ...
PMID:TRK inhibitors in TRK fusion-positive cancers. 3222 35


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