The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers. 

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Recent advances and limitations of mTOR inhibitors in the treatment of cancer

Podophyllotoxin and its derivatives: Potential anticancer agents of natural origin in cancer chemotherapy.

Recent technological advances in nanoscience and material designing have led to the development of point-of-care devices for biomolecule sensing and cancer diagnosis. In situ and portable sensing devices for bedside, diagnosis can effectively improve the patient's clinical outcomes and reduce the mortality rate. Detection of exosomal RNAs by immuno-biochip with increased sensitivity and specificity to diagnose cancer has raised the understanding of the tumor microenvironment and many other technology-based biosensing devices hold great promise for clinical innovations to conquer the unbeatable fort of cancer metastasis. Electrochemical biosensors are the most sensitive category of biomolecule detection sensors with significantly low concentrations down to the atomic level. In this sense, this review addresses the recent advances in cancer detection and diagnosis by developing significant biological sensing devices that are believed to have better sensing potential than existing facilities. 

/pdf/biosensing-chips-for-cancer-diagnosis-and-treatment-a-new-2j2luy59.pdf

Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation

Electrochemical biosensors in exosome analysis; a short journey to the present and future trends in early-stage evaluation of cancers.

Despite the advanced development in the field of drug discovery and design, fighting infectious and non-infectious diseases remains a major worldwide heath challenge due to the limited activity of currently used drugs. Nevertheless, in recent years, the approach of designing nanoparticles for therapeutic applications has gained more interest and promise for future use. Thus, the current study is focused on the evaluation of A. judaica extract and chitosan nanoparticles loaded extract (CNPsLE) for potential antimicrobial and anticancer activities. The HPLC analysis of the extract has shown the presence of various phenolic and flavonoid compounds, including kaempferol (3916.34 µg/mL), apigenin (3794.32 µg/mL), chlorogenic acid (1089.58 µg/mL), quercetin (714.97 µg/mL), vanillin (691.55 µg/mL), naringenin (202.14 µg/mL), and rutin (55.64 µg/mL). The extract alone showed higher MIC values against B. subtilis, E. coli, S. aureus, K. pneumonia, and C. albicans (62.5, 15.65, 15.62, 31.25, and 31.25 µg/mL, respectively), whereas lower MIC values were observed when the extract was combined with CNPsLE (0.97, 1.95, 3.9, 4.1, and 15.62 µg/mL, respectively). The extract exhibited low cytotoxicity against normal Vero cells with IC50 173.74 µg/mL in comparison with the cytotoxicity of the CNPsLE (IC50, 73.89 µg/mL). However, CNPsLE showed more selective toxicity against the human prostate cancer cell line (PC3) with IC50 of 20.8 µg/mL than the extract alone with 76.09 µg/mL. In the docking experiments, kaempferol and apigenin were revealed to be suitable inhibitors for prostate cancer (2Q7L). Overall, the obtained data highlighted the promising potential therapeutic use of CNPsLE as an anticancer and antimicrobial agent.

/pdf/phytochemical-characterization-and-efficacy-of-artemisia-2odhqn77.pdf

Phytochemical Characterization and Efficacy of Artemisia judaica Extract Loaded Chitosan Nanoparticles as Inhibitors of Cancer Proliferation and Microbial Growth

Abstract Over the past few years, the cancer-related disease has had a high mortality rate and incidence worldwide, despite clinical advances in cancer treatment. The drugs used for cancer therapy, have high side effects in addition to the high cost. Subsequently, to reduce these side effects, many studies have suggested the use of natural bioactive compounds. Among these, which have recently attracted the attention of many researchers, quercetin has such properties. Quercetin, a plant flavonoid found in fresh fruits, vegetables and citrus fruits, has anti-cancer properties by inhibiting tumor proliferation, invasion, and tumor metastasis. Several studies have demonstrated the anti-cancer mechanism of quercetin, and these mechanisms are controlled through several signalling pathways within the cancer cell. Pathways involved in this process include apoptotic, p53, NF-κB, MAPK, JAK/STAT, PI3K/AKT, and Wnt/β-catenin pathways. In addition to regulating these pathways, quercetin controls the activity of oncogenic and tumor suppressor ncRNAs. Therefore, in this comprehensive review, we summarized the regulation of these signalling pathways by quercetin. The modulatory role of quercetin in the expression of various miRNAs has also been discussed. Understanding the basic anti-cancer mechanisms of these herbal compounds can help prevent and manage many types of cancer. 

/pdf/potential-mechanisms-of-quercetin-in-cancer-prevention-focus-35mzz7ue.pdf

Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets

https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-022-02677-w

Chemotherapy resistance is a serious pitfall in the treatment of colon cancers (CCs). Previous studies have found that exosomes (Exo) play a pivotal role in tumor drug resistance via the transfer of proteins and genetic materials to the acceptor cells. To date, the mechanisms orchestrating Exo‐derived resistance in cancer cells have been the center of attention. Herein, we aimed to evaluate the role of exosomal nuclear factor erythroid 2‐related factor 2 (Nrf2) on oxaliplatin (1‐OHP) resistance in human colorectal cancer LS174T cells in vitro. To this end, exosomal‐Nrf2‐mediated 1‐OHP resistance was examined using different assays. Exo was isolated from resistant LS174T cells (LS174T/R) and added to the culture medium of sensitive LS174T cells (LS174T/S). According to our data, LS174T/S cells successfully adsorbed PKH26‐Exo driven from LS174T/R cells. Western blotting showed an increased Nrf2 level in Exo isolated from LS174T/R cells compared to LS174T/S cell‐derived Exo (p < .05). The incubation of LS174T/S cells with LS174T/R‐derived Exo increased half‐maximal inhibitory concentration values in response to treatment with 1‐OHP (p < .05). Besides this, the apoptotic changes were diminished in LS174T/S cells after incubation with LS174T/R‐derived Exo. Of note, the exposure of LS174T/S cells to LS174T/R cell‐derived Exo increased the expression of Nrf2 and P‐glycoprotein (P‐gp) compared to the nontreated LS174T/S cells (p < .05). In line with these changes, lower intracellular Rhodamin 123 content was detected in Exo‐treated cells compared to the nontreated LS174T/S cells. Exo increased migration and clonogenic capacity of LS174T/S cells after incubation with Exo‐derived from resistant cells. Of note, inhibition of Nrf2 with a specific blocker, brusatol, blunted these effects. Taken together, Exo‐mediated transfer of Nrf2 is involved in the development of oxaliplatin resistance in CC cells by upregulating P‐gp.

A. P. Tazekand

Papers

Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets

Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets

In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells