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Drugging cancer vulnerabilities toward innovative clinical trials

Drugging image largeGuest Editors: Anna Spreafico1, Lorenza Landi2, Sabrina Strano3
1 - Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
2 - IRCCS Regina Elena National Cancer Institute, Rome, Italy
3 - IRCCS Regina Elena National Cancer Institute, Rome, Italy

Submission deadline: 30th June 2022. Submit your research here.

The study of cancer vulnerabilities remains a colossal challenge in oncology. Substantial advances have been made to identify the genetic makeup of tumor cells and related targets, using large-scale multi-omics approaches and innovative machine learning-based methods.

While non-clinical research is one of the drug discovery’s pillars, several “in vitro” screening methods and “in vivo” models are only suitable for “artificial” conditions, lack reproducibility and cannot be easily applicable in the clinical setting. The identification of cancer-specific dependencies and their translation into clinical utility is essential to implement precision medicine in daily practice.

Clinical trials represent essential resources for drug discovery and drive the “go versus no-go” decision in the development of novel anticancer treatments, laying the foundation for new ways to conquer cancer. Throughout the decades, the concept, design and execution of clinical trials have evolved. From conventional, histology pre-defined, and empirically based investigations, trials have shifted towards selective molecular and blood and/or tumor-based biomarker-driven approaches, that integrate circular pathways (bench-to-bedside-to-bench), cutting-edge technologies, and “smart” real-time reassessment study designs.

Keywords: Treatment, Clinical Trial, Microbiome, Radiomics, Artificial Intelligence, Metabolomics, Epigenomics, Proteomics, DNA/RNA Sequencing, Single Cell Sequencing

This special issue of the Journal of Experimental & Clinical Cancer Research, aims to recognize the pivotal role of experimental therapeutics and translational research, identify existing gaps through real-world, retrospective and prospective data, set priorities for the next generation of scientists, enhance global learning, and delineate a future framework to increase the efficiency of targeting and drugging cancer vulnerabilities in our lifetime.

  1. Characterization of clinical phenotypes in context with tumor and host genomic information can aid in the development of more effective and less toxic risk-adapted and targeted treatment strategies. To analyze...

    Authors: Stefanie V. Junk, Elke Schaeffeler, Martin Zimmermann, Anja Möricke, Rita Beier, Peter Schütte, Birthe Fedders, Julia Alten, Laura Hinze, Norman Klein, Andreas Kulozik, Martina U. Muckenthaler, Rolf Koehler, Arndt Borkhardt, Jayaram Vijayakrishnan, David Ellinghaus…
    Citation: Journal of Experimental & Clinical Cancer Research 2023 42:21
  2. CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotox...

    Authors: Matthew Frigault, Anand Rotte, Ayub Ansari, Bradford Gliner, Christopher Heery and Bijal Shah
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  3. Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Ev...

    Authors: Daniela A. Bota, Thomas H. Taylor, David E. Piccioni, Christopher M. Duma, Renato V. LaRocca, Santosh Kesari, Jose A. Carrillo, Mehrdad Abedi, Robert D. Aiken, Frank P. K. Hsu, Xiao-Tang Kong, Candace Hsieh, Peter G. Bota, Gabriel I. Nistor, Hans S. Keirstead and Robert O. Dillman
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  4. Acute myeloid leukemia (AML) is an aggressive hematological cancer resulting from uncontrolled proliferation of differentiation-blocked myeloid cells. Seventy percent of AML patients are currently not cured wi...

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    Citation: Journal of Experimental & Clinical Cancer Research 2022 41:340
  5. Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However, epigenetic inhibitors show a heteroge...

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  6. Tumour hypoxia is a known and extensively researched phenomenon that occurs in both solid and haematological malignancies. As cancer cells proliferate, demand for oxygen can outstrip supply reducing tumour oxy...

    Authors: Bill Harris, Sana Saleem, Natalie Cook and Emma Searle
    Citation: Journal of Experimental & Clinical Cancer Research 2022 41:318
  7. Medulloblastoma is the most common malignant pediatric brain tumor and group 3 subtype medulloblastoma (G3-MB) exhibits the worst prognosis. Super enhancers (SEs) are large clusters of enhancers that play impo...

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  8. Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic de...

    Authors: Mehrdad Zarei, Omid Hajihassani, Jonathan J. Hue, Hallie J. Graor, Alexander W. Loftus, Moeez Rathore, Ali Vaziri-Gohar, John M. Asara, Jordan M. Winter and Luke D. Rothermel
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  9. As the field of translational ‘omics has progressed, refined classifiers at both genomic and proteomic levels have emerged to decipher the heterogeneity of breast cancer in a clinically-applicable way. The int...

    Authors: Karama Asleh, Nazia Riaz and Torsten O. Nielsen
    Citation: Journal of Experimental & Clinical Cancer Research 2022 41:265
  10. Hepatocellular carcinoma (HCC) remains difficult to treat due to limited effective treatment options. While the proteasome inhibitor bortezomib has shown promising preclinical activity in HCC, clinical trials ...

    Authors: Jhin Jieh Lim, Lissa Hooi, Yock Young Dan, Glenn K. Bonney, Lei Zhou, Pierce K.-H. Chow, Cheng Ean Chee, Tan Boon Toh and Edward K.-H. Chow
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  11. The mechanism by which glioblastoma evades temozolomide (TMZ)-induced cytotoxicity is largely unknown. We hypothesized that mitochondria plays a role in this process.

    Authors: Chia-Hung Chien, Wen-Bin Yang, Jian-Ying Chuang, Jung-Shun Lee, Wei-An Liao, Chih-Yuan Huang, Pin-Yuan Chen, An-Chih Wu, Shun-Tai Yang, Chien-Cheng Lai, Pei-I Chi, Jui-Mei Chu, Siao Muk Cheng, Chan-Chuan Liu, Daw-Yang Hwang, Shang-Hung Chen…
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  12. There is no universally accepted treatment for patients with advanced papillary renal cell carcinoma (PRCC). The presence of activating mutations in MET, as well as gain of chromosome 7, where the MET gene is loc...

    Authors: Roma Pahwa, Janhavi Dubhashi, Anand Singh, Parthav Jailwala, Alexei Lobanov, Craig J. Thomas, Michele Ceribelli, Kelli Wilson, Christopher J. Ricketts, Cathy D. Vocke, Catherine Wells, Donald P. Bottaro, W. Marston Linehan, Len Neckers and Ramaprasad Srinivasan
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  14. Trametinib is an oral MEK 1/2 inhibitor, with a single agent recommended phase 2 dose (RP2D) of 2 mg daily (QD). This study was designed to evaluate RP2D, maximum tolerated dose (MTD), and pharmacokinetic (PK)...

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  15. High-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene ...

    Authors: Marianna Buttarelli, Alessandra Ciucci, Fernando Palluzzi, Giuseppina Raspaglio, Claudia Marchetti, Emanuele Perrone, Angelo Minucci, Luciano Giacò, Anna Fagotti, Giovanni Scambia and Daniela Gallo
    Citation: Journal of Experimental & Clinical Cancer Research 2022 41:50
  16. The RAS oncogene is both the most frequently mutated oncogene in human cancer and the first confirmed human oncogene to be discovered in 1982. After decades of research, in 2013, the Shokat lab achieved a seminal...

    Authors: Albert K. Kwan, Gary A. Piazza, Adam B. Keeton and Caio A. Leite
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  17. Emerging evidence from the numerous clinical trials involving cytokine-induced killer (CIK) cell therapy suggests that its optimization in combination with other contemporary cancer therapies in a complementar...

    Authors: Amit Sharma and Ingo G. H. Schmidt-Wolf
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  18. Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would pro...

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  19. Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumours worldwide. Sorafenib (SOR) is one of the most effective single-drug systemic therapy against advanced HCC, but the identifi...

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    The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2022 41:40

  20. The hopeful outcomes from 30 years of research in BH3-mimetics have indeed served a number of solid paradigms for targeting intermediates from the apoptosis pathway in a variety of diseased states. Not only ha...

    Authors: Paul A. Townsend, Maria V. Kozhevnikova, Olivier N. F. Cexus, Andrey A. Zamyatnin Jr and Surinder M. Soond
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    Authors: Hao Zhou, Wei Liu, Yongming Zhou, Zhenya Hong, Jian Ni, Xiaoping Zhang, Ziping Li, Mengyuan Li, Wenjuan He, Donghua Zhang, Xuexing Chen and Jianhua Zhu
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  22. Glioblastoma (GBM; grade IV glioma) is characterized by a very short overall survival time and extremely low 5-year survival rates. We intend to promote experimental and clinical research on rationale and scie...

    Authors: Silvia Matteoni, Paola Matarrese, Barbara Ascione, Lucia Ricci-Vitiani, Roberto Pallini, Veronica Villani, Andrea Pace, Marco G. Paggi and Claudia Abbruzzese
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  23. Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safet...

    Authors: Franziska Böttger, Andrea Vallés-Martí, Loraine Cahn and Connie R. Jimenez
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  24. Patients with ovarian cancer often present at advanced stage and, following initial treatment success, develop recurrent drug-resistant disease. PARP inhibitors (PARPi) are yielding unprecedented survival bene...

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  26. The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the develop...

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  27. The exploitation of novel nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is challenging for tumor theranostics.

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  30. Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic com...

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  31. Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on t...

    Authors: Guo-Hua Li, Qiang Qu, Ting-Ting Qi, Xin-Qi Teng, Hai-Hong Zhu, Jiao-Jiao Wang, Qiong Lu and Jian Qu
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