- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
Identification of combination partners to combat acquired resistance to ulixertinib (ERK1/2 inhibitor) using transcriptomics (Section 25) - Mar 9, 2022 - Abstract #AACR2022AACR_2673; P1 We also validated combinations with autophagy inhibitors, one of which is now being tested in a Phase I clinical trial (NCT04145297).In summary, we have identified some potential resistance mechanisms to ulixertinib and have validated key genes/pathways which may act as synergistic combination targets. This work not only informs future clinical development for ulixertinib but also improves our understanding of the complex interplay between the MAPK and other signaling pathways.
- |||||||||| gefitinib / Generic mfg.
Journal: SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer. (Pubmed Central) - Mar 8, 2022 Consistently, the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples. Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis, thereby offering a novel avenue for potential cancer therapeutics.
- |||||||||| Journal: Corilagin induces apoptosis and inhibits autophagy of HL‑60 cells by regulating miR‑451/HMGB1 axis. (Pubmed Central) - Mar 8, 2022
Furthermore, knockdown of miR‑451 also attenuated corilagin‑induced proliferation inhibition of HL‑60 cells, implying that miR‑451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL‑60 cells by regulating the miR‑451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.
- |||||||||| cisplatin / Generic mfg.
Biomarker, Journal: Role of Organic Cation Transporter 2 in Autophagy Induced by Platinum Derivatives. (Pubmed Central) - Mar 8, 2022 Furthermore, inhibition of autophagy is associated with higher toxicity of platinum derivatives, and starvation was found to offer protection against cisplatin-associated toxicity. In conclusion, activation of autophagy could be a potential strategy to protect against unwanted toxicities induced by treatment with platinum derivatives.
- |||||||||| Review, Journal: Role of autophagy in drug resistance and regulation of osteosarcoma (Review). (Pubmed Central) - Mar 8, 2022
Autophagy is considered an important mechanism through which bone tumor cells escape apoptosis; inhibition of autophagy may significantly increase the sensitivity of tumor cells to chemotherapeutic drugs. The present review discusses the relationship between chemotherapy resistance and autophagy-related genes, the regulation of autophagy in OS, as well as drugs that inhibit protective autophagy in tumors or cause autophagic death of OS cells or increase their sensitivity to chemotherapy drugs, thereby reducing chemotherapy resistance and increasing efficacy.
- |||||||||| Journal: Zearalenone Exposure Disrupts Blood-Testis Barrier Integrity through Excessive Ca-Mediated Autophagy. (Pubmed Central) - Mar 5, 2022
Meanwhile, inhibition of autophagy by CQ and 3-MA or inhibition of cytoplasmic Ca by BAPTA-AM was sufficient to reduce the effects of ZEA on the TM4 cell BTB. To summarize, this study emphasizes the role of Ca-mediated autophagy in ZEA-induced BTB destruction, which deepens our understanding of the molecular mechanism of ZEA-induced male reproductive disorders.
- |||||||||| Journal: Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps. (Pubmed Central) - Mar 5, 2022
Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.
- |||||||||| Journal: The role of autophagy in metal-induced urogenital carcinogenesis. (Pubmed Central) - Mar 4, 2022
Albeit few, recent experimental studies have shown that As and Cd promote tumorigenesis via autophagy and that inhibition of autophagic signaling suppressed metal-induced carcinogenesis. In light of the newly emerging role of autophagic involvement in metal-induced carcinogenesis, the present review focuses explicitly on the mechanistic role of autophagy and potential signaling pathways involved in As-, Cd-, and Cr-induced urogenital carcinogenesis.
- |||||||||| buparlisib (BKM120) / Novartis, Adlai Nortye
Clinical, Journal, BRCA Biomarker: Hydroxychloroquine synergizes with the PI3K inhibitor BKM120 to exhibit antitumor efficacy independent of autophagy. (Pubmed Central) - Mar 4, 2022 Our study revealed that HCQ and BKM120 synergistically increased DSBs in tumor cells and therefore augmented apoptosis, resulting in enhanced antitumor efficacy. Our findings provide a new insight into how HCQ exhibits antitumor efficacy and synergizes with PI3Ki BKM120, and warn that one should consider the "off target" effects of HCQ when used as autophagy inhibitor in the clinical treatment of cancer.
- |||||||||| Journal: The nutrient sensor mTORC1 regulates insulin secretion by modulating ß-cell autophagy. (Pubmed Central) - Mar 4, 2022
In the fasting state, autophagy is regulated in an mTORC1-dependent manner and its stimulation is required to keep insulin levels low, thereby preventing hypoglycemia. Reciprocally, stimulation of mTORC1 by elevated leucine and glucose, which is common in obesity, may promote hyperinsulinemia by inhibiting autophagy.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Autophagy-inhibiting biomimetic nanodrugs enhance photothermal therapy and boost antitumor immunity. (Pubmed Central) - Mar 4, 2022 In this study, we fabricated coassembled photothermal agents (indocyanine green, ICG) and autophagy inhibitors (chloroquine, CQ) and red blood cell and cancer cell hybrid membrane (RCm)-camouflaged ICGCQ@RCm nanoparticles (ICGCQ@RCm NPs) to enhance tumor LTPTT...Furthermore, the ICGCQ@RCm NPs showed high biosafety in vitro and in vivo. The ICGCQ@RCm NPs demonstrated tumor-targeting and imaging-guided autophagy inhibition-sensitized LTPTT using two Food and Drug Administration (FDA)-approved drugs, which have great potential for clinical application.
- |||||||||| sirolimus / Generic mfg.
Journal: Berberine Influences the Survival of Fat Grafting by Inhibiting Autophagy and Apoptosis of Human Adipose Derived Mesenchymal Stem Cells. (Pubmed Central) - Mar 3, 2022 The autophagy promoter rapamycin and autophagy inhibitor 3-MA were incubated separately to investigate the crosstalk between autophagy and apoptosis...The treated human-derived adipose tissue was transplanted into BALB/c nude mice, and with the intervention of BBR, the fat grafting had a higher survival rate, lower inflammatory cell infiltration and fibrosis level. Our present study revealed that BBR was a promising anti-autophagy and apoptosis agent for improving the survival rate of ADSCs during cell transplantation.
- |||||||||| cisplatin / Generic mfg.
Journal: Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy. (Pubmed Central) - Mar 3, 2022 Mechanistically, we showed that the effect of trehalose was attributed to increased nuclear translocation of transcription factor EB (TFEB), and this effect could be mimicked by TFEB overexpression and inhibited by TFEB gene silencing or treatment with cyclosporin A (CsA), a calcineurin inhibitor. Taken together, our findings suggest that trehalose and autophagy play a role in protecting against cisplatin-induced ototoxicity and that pharmacological enhancement of TFEB-mediated autophagy is a potential treatment for cisplatin-induced damage in cochlear HCs and HEI-OC1 cells.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: Autophagy inhibitors alleviate Japanese encephalitis virus-induced cerebral inflammation in mice. (Pubmed Central) - Mar 3, 2022 No significant difference was observed in the expression of the PI3K/AKT/NF-κB pathway in mouse brain among the different groups. Our study suggests that the autophagy inhibitors Wort and CQ reduce JEV infection and weaken the inflammatory response, which does not depend on the PI3K/AKT/NF-κB pathway in mouse brain.
- |||||||||| Review, Journal: Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology. (Pubmed Central) - Mar 1, 2022
Their further preclinical and clinical development should follow the same stringent rules as for any other synthetic drug as well. Prospective randomized, placebo-controlled clinical phase I and II trials should be initiated to unravel the full potential of plant alkaloids for drug repositioning.
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