Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells

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What a great day! One of our youngest, Kristóf Felegyi just placed another brick in the wall of his PhD with this article about isolating and identifying novel polyporenic acids and triterpenes from Buglossoporus quercinus. The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.
Nice work and way to go, Kristof!

JoF | Free Full-Text | Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells (mdpi.com)

Novel targets for immune-checkpoint inhibition in cancer

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Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer, highlight their biology, emphasizes the current understanding of resistance mechanisms, and focuses on promising strategies that are under investigation. Current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients are also collected.

Novel targets for immune-checkpoint inhibition in cancer – Cancer Treatment Reviews

2-Hydroxypropyl-β-cyclodextrin (HPβCD) as a Potential Therapeutic Agent for Breast Cancer

Today's cyclodextrin,

today’s cyclodextrin:
Breast cancer is a global burden with the most severe subtype being triple-negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule. Treatment with the cholesterol-depletory agent 2-hydroxypropyl-β-cyclodextrin (HPβCD) impeded the growth of cancer cells and further led to cancer cell death, which could be attributed to an altered cellular cholesterol profile following treatment. Furthermore, mice xenograft studies indicated complete eradication of early-stage tumours with no relapse, followed by a remarkable reduction in intermediate- and late-stage tumours, respectively. SFRP1 was identified as a possible molecular target facilitating the therapeutic action of HPβCD. These findings consequently potentiate cholesterol depletion as a novel anticancer strategy to be pursued.

University of the Witwatersrand – Tawanda Ziningav Reubina Wadee, Mandeep Kaur et al

See the full article here

Mechanisms of cancer resistance in long-lived mammals

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Have you known that certain animals are unable to develop cancer? Do you also know why?

Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly, and are highly prone to cancer. They have been very useful for modeling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique traits of very high value to humans, such as cancer resistance and longevity. In recent years, several discoveries have been made in non-standard mammalian species, providing new insights into the natural mechanisms of cancer resistance. These include mechanisms of cancer resistance in the naked mole rat, blind mole rat, and elephant. In each of these species, evolution took a different path, leading to novel mechanisms. Many other long-lived mammalian species display cancer resistance, including whales, grey squirrels, microbats, cows, and horses. Understanding the molecular mechanisms of cancer resistance in all these species is important and timely, as, ultimately, these mechanisms could be harnessed for the development of human cancer therapies.

See the full article here on nature.com

Reduction of thyroid radioactive iodine exposure by oral administration of cyclic oligosaccharides

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Radioactive iodine may cause thyroid cancer and hypofunction and accordingly must be properly managed. If the absorption of radioactive iodine is suppressed, it can be expected to lead to a reduction in thyroid exposure. This study the inhibition of radioactive iodine absorption by the oral administration of α-cyclodextrin is shown in a murine model. The uptake of radioactive iodine into the thyroid gland in mice administered with radioactive iodine and an α-cyclodextrin solution was approximately 40% lower after 24 h. The finding that oral uptake of α-cyclodextrin has an inhibitory effect on the transfer of radioactive iodine to the thyroid gland has potential for application in many fields such as food, pharmaceuticals, nuclear emergency preparedness, and medicine.
Kumamoto University, JAPAN

See the full article on nature.com

A saliva-specific fucosylated structure-based sugar profile

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A saliva-specific fucosylated structure-based sugar profile seems to be an efficent cancer diagnostic tool as claimed by Soochow University.
From the human saliva sample proteins extracted, subjected to enzymolysis and enriched in glycans from glycoproteins. Structural analysis and quantitative analysis of abundance on the glycans by means of mass spectrometry determines a glycan profile in the sample. By analyzing healthy saliva, non-cancer saliva, and lung cancer saliva, sugar profiles of high-abundance core fucose and branched fucose are identified. The method can be applied to clinical screening of lung cancer. The saliva-specific fucosylated structure-based sugar profile and the detection method therefor facilitate early diagnosis, feature easy-to-collect samples, and are not harmful to a patient, and thus have an excellent application prospect and important significance in the aspects of early screening and treatment of high-morbidity and high-death-rate lung cancer.

See the full patent here

Insights into recent preclinical studies on labeled cyclodextrin-based imaging probes: Towards a novel oncological era

Today's cyclodextrin,

today’s cyclodextrin:
is a beautiful review on labeled CD-based imaging probes from University of Debrecen (Zita Képes, István Hajdu, Ferenc Fenyvesi, and György Trencsényi).
As malignancies remain one of the major health concerns worldwide, increasing focus has been centered on the application of cyclodextrins (CDs) in cancer imaging and therapy due to their outstanding inclusion-forming capability. Studies applying fluorescently- CDs, or CD-based MRI contrast agents revealed much about pharmacokinetics and diagnostic applications; however, derivatives labeled with positron emitters seem superior molecular probes in the investigation of the route of CDs in the biological niche. Exploiting the firm signaling interaction between cancer-related cyclooxygenase-2, prostaglandin E2 (PGE2), and RAS oncoprotein, radioconjugated, PGE2-affine CDs project the establishment of novel imaging probes and therapeutic agents. 

See the full article here: Insights into recent preclinical studies on labelled cyclodextrin-based imaging probes: Towards a novel oncological era

Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery

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Today’s cyclodextrin:
Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery
Although cyclodextrin-based renal-clearable nanocarriers have a high potential for clinical translation in targeted cancer therapy, their designs remain to be optimized for tumor retention. Here Seoul National University and Chungnam National University report on the design of renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery. The optimized cyclodextrin shows a high tumor accumulation and is used for the delivery of doxorubicin and ulixertinib. Higher tumor accumulation and tumor penetration facilitate tumor elimination. The improved antitumor efficacy is demonstrated in heterotopic and orthotopic colorectal cancer models.

See the full article here: Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery

Lipid-based RNA formulations suitable for therapy

Today's cyclodextrin, , , ,

today’s cyclodextrin:
In this invention, BioNTech SE provides a method of producing a composition comprising RNA lipoplex particles. The main focus of the description is antitumoral therapy.
In the formulation itself, the aqueous colloidal suspension of liposomes is combined with an aqueous solution comprising RNA, thereby producing the composition comprising RNA lipoplex particles. The formulation requires frozen storage conditions; hence the use of cyroprotectant is necessary. The invention proposes mono- di- and oligosaccharides to protect such compositions, including various cyclodextrins and cyclodextrin polymers.
The use of cyclodextrins as cryoprotectants and stabilizers in biopharmaceutical formulations is an emerging technology.

Dr. Hossam Hefesha, Heinrich Haas, Ferdia Bates, Christian Hotz
Katalin Karikó

See the full patent Patentscope