Recent patents on anti-cancer drug discovery最新文献

Background: It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects.

Objective: This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor.

Methods: Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs.

Results: Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment.

Conclusion: In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Objective: This paper aims to review studies regarding side effects found during Non-Hodgkin Lymphoma treatment, to suggest the drug class most associated with these effects, as well as the most prevalent side effect grade.

Methods: This review is registered in PROSPERO (IDCRD42022295774) and followed the PICOS strategy and PRISMA guidelines. The search was carried out in the databases PubMed/MEDLINE, Scientific Electronic Library Online, and DOAJ. Medical Subject Headings Terms were used and quantitative studies with conclusive results regarding side effects during the non-Hodgkin lymphoma treatment were selected. Patent information was obtained from google patents.

Results: Monoclonal antibodies were the main drug class associated with side effects during NHL therapy. The combination of Rituximab (Rituxan®; patent EP1616572B) and iInotuzumab (Besponsa®; patent EP1504035B3) was associated with a higher incidence of thrombocytopenia (p<0.05), while the combination of Rituximab and Venetoclax (Venclexta®; patent CN107089981A) was associated with a higher incidence of neutropenia (p<0.05) when compared to Bendamustine combinations (Treanda ™; patent US20130253025A1). Meta-analysis revealed a high prevalence of grade 3-4 neutropenia and thrombocytopenia in men. Finally, Americans and Canadians experienced a higher prevalence of these side effects, when compared to others nationalities (p<0.05).

Conclusion: Patents regarding the use of monoclonal antibodies in NHL treatment were published in the last year. Monoclonal antibodies associated with neutropenia (grade 3-4) and thrombocytopenia, especially in North American men treated for NHL, and with an average age of 62 years demonstrated importance in this study.

Background: Solid tumors such as colon cancer are characterized by rapid and sustained cell proliferation, which ultimately results in hypoxia, induction of hypoxia-inducible factor-1α (HIF-1α), and activation of glycolysis to promote tumor survival and immune evasion. We hypothesized that a combinatorial approach of menadione (MEN) as an indirect HIF-1α inhibitor and sodium oxamate (OX) as a glycolysis inhibitor may be a promising treatment strategy for colon cancer.

Objectives: We investigated the potential efficacy of this combination for promoting an antitumor immune response and suppressing tumor growth in a rat model of colon cancer.

Methods: Colon cancer was induced by once-weekly subcutaneous injection of 20 mg/kg dimethylhydrazine (DMH) for 16 weeks. Control rats received the vehicle and then no further treatment (negative control) or MEN plus OX for 4 weeks (drug control). Dimethylhydrazine-treated rats were then randomly allocated to four groups: DMH alone group and other groups treated with MEN, OX, and a combination of (MEN and OX) for 4 weeks. Serum samples were assayed for the tumor marker carbohydrate antigen (CA19.9), while expression levels of HIF-1α, caspase-3, PHD3, LDH, and PD1 were evaluated in colon tissue samples by immunoassay and qRT-PCR. Additionally, Ki-67 and Siah2 expression levels were examined by immunohistochemistry.

Results: The combination of MEN plus OX demonstrated a greater inhibitory effect on the expression levels of HIF-1α, Siah2, LDH, Ki-67, and PD1, and greater enhancement of caspase-3 and PHD3 expression in colon cancer tissues than either drug alone.

Conclusion: Simultaneous targeting of hypoxia and glycolysis pathways by a combination of MEN and OX could be a promising therapy for inhibiting colon cancer cell growth and promoting antitumor immunity [1].

Introduction: Fatty acid synthase (FASN), is a key metabolic enzyme involved in fatty acid biosynthesis and is an essential target for multiple disease progressions like cancer, obesity, NAFLD, etc. Aberrant expression of FASN is associated with deregulated energy metabolism of cells in these diseases.

Area covered: This article provides a summary of the most recent developments in the discovery of novel FASN inhibitors with potential therapeutic uses in cancer, obesity, and other metabolic disorders such as nonalcoholic fatty liver disease from 2016 to the present. The recently published patent applications and forthcoming clinical data of FASN inhibitors from both academia and the pharma industries are also highlighted in this study.

Expert opinion: The implication of FASN in multiple diseases has provided an impetus for developing novel inhibitors by both pharma companies and academia. Critical analysis of the patent literature reveals the exploration of diverse molecular scaffolds to identify potential FASN inhibitors that target the different catalytic domains of the enzyme. In spite of these multifaceted efforts, only one molecule, TVB-2640, has reached phase II trials for nonalcoholic steatohepatitis (NASH) and many malignancies. However, thecombined efforts of pharma companies to produce several FASN inhibitors might facilitate the clinical translation of this unique class of inhibitors. Nevertheless, concerted efforts towards developing multiple FASN inhibitors by pharma companies might facilitate the clinical translation of this novel class of inhibitors.