An Open Access Database of Licensed Cancer Drugs

Pantziarka, Pan; Capistrano, Rica; Potter, Arno De; Vandeborne, Liese; Bouche, Gauthier

doi:10.3389/fphar.2021.627574

Cited by 40 publications

(23 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These 99 patients harbor identical tumors in terms of the altered molecular processes they possess and should therefore be treated in a similar manner. Table S4 lists suggested combined treatments for each patient based on PaSSS and available, FDA-approved anti-cancer drugs 28 . In general, once PaSSS is determined, a clinician can select the specific drug targets based on practical considerations, such as inhibitor availability, drug costs, toxicity and drug interactions in the combined treatment.…”

Section: Resultsmentioning

confidence: 99%

“…These 61 subtypes of HNSCC tumors, each representing a signaling barcode, are assigned patient-tailored combinations of drugs, many of which already exist in clinics for the treatment of different types of cancer. For example lapatinib (dual anti-EGFR and HER2 inhibitor), used for the treatment of breast cancer 28 , appears frequently in PaSSS analysis as a suggested drug in mono- or combined treatments for HNSCC. Another example includes crizotinib (anti-cMet inhibitor, approved for the treatment of lung cancer) that appears in certain cases, usually in combination with lapatinib, as a suggested drug for HNSCC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Gene expression data of HNSCC tissues treated with cetuximab can be found at GEO database, (GSE109756). Anti-cancer drugs used to design PaSSS combinations ( Table S4 ) can be found in https://www.anticancerfund.org/en/cancerdrugs-db 28 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes

Jubran¹,

Vilenski²,

Flashner-Abramson³

et al. 2022

Theranostics

View full text Add to dashboard Cite

Therapeutic strategies for advanced head and neck squamous carcinoma (HNSCC) consist of multimodal treatment, including Epidermal Growth Factor Receptor (EGFR) inhibition, immune-checkpoint inhibition, and radio (chemo) therapy. Although over 90% of HNSCC tumors overexpress EGFR, attempts to replace cytotoxic treatments with anti-EGFR agents have failed due to alternative signaling pathways and inter-tumor heterogeneity. Methods: Using protein expression data obtained from hundreds of HNSCC tissues and cell lines we compute individualized signaling signatures using an information-theoretic approach. The approach maps each HNSCC malignancy according to the protein-protein network reorganization in every tumor. We show that each patient-specific signaling signature (PaSSS) includes several distinct altered signaling subnetworks. Based on the resolved PaSSSs we design personalized drug combinations. Results: We show that simultaneous targeting of central hub proteins from each altered subnetwork is essential to selectively enhance the response of HNSCC tumors to anti-EGFR therapy and inhibit tumor growth. Furthermore, we demonstrate that the PaSSS-based drug combinations lead to induced expression of T cell markers and IFN-γ secretion, pointing to higher efficiency of the immune response. Conclusion: The PaSSS-based approach advances our understanding of how individualized therapies should be tailored to HNSCC tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes

Jubran¹,

Vilenski²,

Flashner-Abramson³

et al. 2022

Theranostics

View full text Add to dashboard Cite

show abstract

“…Open access journals and databases are an essential basis for drug target developments. Endeavours, like the TCGA database and Oncomine (Rhodes et al, 2004) has contributed vastly to accelerate drug research in oncology the latest decade and concurrently multiple other enterprises emerged to assist researchers with valuable genomic, transcriptomic and proteomic data in the pursue for novel cancer biomarkers (Krempel et al, 2018;Wishart et al, 2021;Banck et al, 2021;Pantziarka et al, 2021). However, the information is not well structured for speci c diseases, including rare and highly progressive cancers (Gadaleta et al, 2011;Creighton 2018).…”

Section: Discussionmentioning

confidence: 99%

Project SCANCER: An Open-access Drug Repurposing and Data-mining Platform to Enhance Target Validation and Optimize International Research Efforts against Highly Progressive Cancers

Dora

Dóra

Szegvari

et al. 2022

Preprint

View full text Add to dashboard Cite

The expanding body of potential therapeutic targets requires easily accessible, structured, and transparent real-time interpretation of molecular data. We invite research teams to join and aim to enhance the cooperative work of more experienced groups to harmonize international efforts to overcome less prevalent, devastating malignancies. We show how we integrated our previous expertise in small-cell lung cancer (SCLC) with data mining approaches to initiate a new platform to overcome highly progressive cancers such as triple-negative breast and pancreatic cancer. Here, we integrate available fundamental data and present a novel, open access, data-mining, drug repurposing platform, deriving our searches from the entries of Clue.io. Through the front end, users can create their drug-target list to select the clinically most relevant targets for further functional validation assays or drug trials. SCANCER integrates searches from publicly available databases, such as PubChem, Drug Bank, PubMed, and EMA; and complementing them with background information on compounds using entities like UniProt, String, and genecards. Cancer drug discovery requires a convergence of complex, often disparate fields. We present a simple, transparent, and user-friendly drug repurposing database.

show abstract

“…Moreover, repurposed drugs may reveal new targets and pathways that can be further exploited. Thus, drug repurposing is a promising approach in oncology for the development of new treatments [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Mechanism of Action of Spiperone—A Candidate for Drug Repurposing for Colorectal Cancer

Antona

Varalda

Roy

et al. 2022

Cancers

View full text Add to dashboard Cite

Approximately 50% of colorectal cancer (CRC) patients still die from recurrence and metastatic disease, highlighting the need for novel therapeutic strategies. Drug repurposing is attracting increasing attention because, compared to traditional de novo drug discovery processes, it may reduce drug development periods and costs. Epidemiological and preclinical evidence support the antitumor activity of antipsychotic drugs. Herein, we dissect the mechanism of action of the typical antipsychotic spiperone in CRC. Spiperone can reduce the clonogenic potential of stem-like CRC cells (CRC-SCs) and induce cell cycle arrest and apoptosis, in both differentiated and CRC-SCs, at clinically relevant concentrations whose toxicity is negligible for non-neoplastic cells. Analysis of intracellular Ca2+ kinetics upon spiperone treatment revealed a massive phospholipase C (PLC)-dependent endoplasmic reticulum (ER) Ca2+ release, resulting in ER Ca2+ homeostasis disruption. RNA sequencing revealed unfolded protein response (UPR) activation, ER stress, and induction of apoptosis, along with IRE1-dependent decay of mRNA (RIDD) activation. Lipidomic analysis showed a significant alteration of lipid profile and, in particular, of sphingolipids. Damage to the Golgi apparatus was also observed. Our data suggest that spiperone can represent an effective drug in the treatment of CRC, and that ER stress induction, along with lipid metabolism alteration, represents effective druggable pathways in CRC.

show abstract

An Open Access Database of Licensed Cancer Drugs

Cited by 40 publications

References 16 publications

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes

Project SCANCER: An Open-access Drug Repurposing and Data-mining Platform to Enhance Target Validation and Optimize International Research Efforts against Highly Progressive Cancers

Dissecting the Mechanism of Action of Spiperone—A Candidate for Drug Repurposing for Colorectal Cancer

Contact Info

Product

Resources

About