Onco | Special Issue : Feature Papers in Onco

Research

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23 pages, 2866 KiB

Open AccessArticle

ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma

by Fatih M. Uckun and Sanjive Qazi

Onco 2022, 2(4), 282-304; https://doi.org/10.3390/onco2040016 - 14 Oct 2022

Cited by 5 | Viewed by 3078

Abstract

Our main objective was to identify abundantly expressed tyrosine kinases in multiple myeloma (MM) as potential therapeutic targets. We first compared the transcriptomes of malignant plasma cells from newly diagnosed MM patients who were risk-categorized based on the patient-specific EMC-92/SKY-92 gene expression signature [...] Read more.

Our main objective was to identify abundantly expressed tyrosine kinases in multiple myeloma (MM) as potential therapeutic targets. We first compared the transcriptomes of malignant plasma cells from newly diagnosed MM patients who were risk-categorized based on the patient-specific EMC-92/SKY-92 gene expression signature values vs. normal plasma cells from healthy volunteers using archived datasets from the HOVON65/GMMG-HD4 randomized Phase 3 study evaluating the clinical efficacy of bortezomib induction/maintenance versus classic cytotoxic drugs and thalidomide maintenance. In particular, ERBB1/EGFR was significantly overexpressed in MM cells in comparison to normal control plasma cells, and it was differentially overexpressed in MM cells from high-risk patients. Amplified expression of EGFR/ERBB1 mRNA in MM cells was positively correlated with increased expression levels of mRNAs for several DNA binding proteins and transcription factors with known upregulating activity on EGFR/ERBB1 gene expression. MM patients with the highest ERBB1/EGFR expression level had significantly shorter PFS and OS times than patients with the lowest ERBB1/EGFR expression level. High expression levels of EGFR/ERBB1 were associated with significantly increased hazard ratios for unfavorable PFS and OS outcomes in both univariate and multivariate Cox proportional hazards models. The impact of high EGFR/ERBB1 expression on the PFS and OS outcomes remained significant even after accounting for the prognostic effects of other covariates. These results regarding the prognostic effect of EGFR/ERBB1 expression were validated using the MMRF-CoMMpass RNAseq dataset generated in patients treated with more recently applied drug combinations included in contemporary induction regimens. Our findings provide new insights regarding the molecular mechanism and potential clinical significance of upregulated EGFR/ERBB1 expression in MM. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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19 pages, 5156 KiB

Open AccessArticle

Augmented Expression of the IL3RA/CD123 Gene in MLL/KMT2A-Rearranged Pediatric AML and Infant ALL

by Sanjive Qazi and Fatih M. Uckun

Onco 2022, 2(3), 245-263; https://doi.org/10.3390/onco2030014 - 25 Aug 2022

Viewed by 2446

Abstract

Here, we evaluated transcript-level IL3RA/CD123 expression in mixed lineage leukemia 1 (MLL) gene/KMT2A-rearranged (MLL-R⁺) vs. MLL-R⁻ pediatric AML as well as infant ALL by comparing the archived datasets of the transcriptomes of primary leukemic cells from the corresponding patient populations. [...] Read more.

Here, we evaluated transcript-level IL3RA/CD123 expression in mixed lineage leukemia 1 (MLL) gene/KMT2A-rearranged (MLL-R⁺) vs. MLL-R⁻ pediatric AML as well as infant ALL by comparing the archived datasets of the transcriptomes of primary leukemic cells from the corresponding patient populations. Our studies provide unprecedented evidence that IL3RA/CD123 expression exhibits transcript-level amplification in MLL-R⁺ pediatric AML and infant ALL cells. IL3RA was differentially upregulated in MLL-AF10⁺ (2.41-fold higher, p-value = 4.4 × 10⁻⁶) and MLL-AF6⁺ (1.83-fold higher, p-value = 9.9 × 10⁻⁴) but not in MLL-AF9⁺ cases compared to other pediatric AML cases. We also show that IL3RA/CD123 expression is differentially amplified in MLL-AF4⁺ (1.76-fold higher, p-value = 2.1 × 10⁻⁴) as well as MLL-ENL⁺ infant ALL (1.43-fold higher, p-value = 0.055). The upregulated expression of IL3RA/CD123 in MLL-R⁺ pediatric AML and infant ALL suggests that CD123 may be a suitable target for biotherapy in these high-risk leukemias. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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19 pages, 41674 KiB

Open AccessArticle

Fucoxanthinol Promotes Apoptosis in MCF-7 and MDA-MB-231 Cells by Attenuating Laminins–Integrins Axis

by Ayaka Yasuda, Momoka Wagatsuma, Wataru Murase, Atsuhito Kubota, Hiroyuki Kojima, Tohru Ohta, Junichi Hamada, Hayato Maeda and Masaru Terasaki

Onco 2022, 2(3), 145-163; https://doi.org/10.3390/onco2030010 - 8 Jul 2022

Cited by 3 | Viewed by 2656

Abstract

Fucoxanthinol (FxOH), the main metabolite of the marine carotenoid fucoxanthin, exerts anti-cancer effects. However, fragmentary information is available on the growth-inhibiting effects of FxOH on breast cancer (BC). We investigated the growth-inhibiting effects of FxOH on human BC cells (MCF-7 and MDA-MB-231 cells), [...] Read more.

Fucoxanthinol (FxOH), the main metabolite of the marine carotenoid fucoxanthin, exerts anti-cancer effects. However, fragmentary information is available on the growth-inhibiting effects of FxOH on breast cancer (BC). We investigated the growth-inhibiting effects of FxOH on human BC cells (MCF-7 and MDA-MB-231 cells), and the underlying mechanisms, differently from previous studies, by using comprehensive transcriptome analysis. The molecular mechanisms of FxOH were evaluated using flow cytometry, microarray, Western blotting, and gene knockdown analyses. FxOH (20 μM) significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. Transcriptome analysis revealed that FxOH modulated the following 12 signaling pathways: extracellular matrix (ECM), adhesion, cell cycle, chemokine and cytokine, PI3K/AKT, STAT, TGF-β, MAPK, NF-κB, RAS/Rho, DNA repair, and apoptosis signals. FxOH downregulated the levels of laminin β1, integrin α5, integrin β1, integrin β4, cyclin D1, Rho A, phosphorylated (p)paxillin (Tyr³¹), pSTAT3(Ser⁷²⁷), and pSmad2(Ser^465/467), which play critical roles in the 12 signaling pathways mentioned above. Additionally, FxOH upregulated the levels of pERK1/2(Thr²⁰²/Tyr²⁰⁴) and active form of caspase-3. Integrin β1 or β4 knockdown significantly inhibited the growth of MCF7 and MDA-MB-231 cells. These results suggest that FxOH induces apoptosis in human BC cells through some core signals, especially the ECM–integrins axis, and the downstream of cell cycle, STAT, TGF-β, RAS/Rho, MAPK, and/or DNA repair signals. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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15 pages, 2879 KiB

Open AccessArticle

Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids

by Tristan Le Clainche, Nazareth Milagros Carigga Gutierrez, Núria Pujol-Solé, Jean-Luc Coll and Mans Broekgaarden

Onco 2022, 2(1), 19-33; https://doi.org/10.3390/onco2010002 - 7 Jan 2022

Cited by 6 | Viewed by 3773

Abstract

Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers [...] Read more.

Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm²), and the dose rate (fluence rate in mW/cm²). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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18 pages, 2219 KiB

Open AccessArticle

Core Needle Biopsy Enhances the Activity of the CCL2/CCR2 Pathway in the Microenvironment of Invasive Breast Cancer

by Marja Heiskala, Kristiina Joensuu and Päivi Heikkilä

Onco 2022, 2(1), 1-18; https://doi.org/10.3390/onco2010001 - 30 Dec 2021

Cited by 2 | Viewed by 2972

Abstract

The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative [...] Read more.

The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative biopsies to increase tumor supportive elements in the microenvironment, whereas, in humans, the impact of CNB on the host’s immunologic response has not been investigated. In this pilot study, we compared the expression of CCL2/CCR2 pathway components at the protein level in samples from CNBs to those from the corresponding resected tumors from 52 patients with primary breast cancer. We found an increased expression of CD163, CD14 and CCR2 in monocytes/macrophages and a slight decrease of CCL2 in the malignant epithelium in the tumors after the biopsy. The increased infiltration of immunosuppressive monocytes/macrophages and the decreased tumor cell CCL2 expression, presumably due to the CCR2 availability-dependent CCL2 internalization, suggest that CNB enhances the activity of the CCL2/CCR2 pathway, and this finding warrants confirmatory examination. The switch in the context-dependent role of CCL2 on the polarization of macrophages may lead to increased tumor supportive function both locally and in the peripheral immune machinery. The future directions in breast cancer should include early interventions to support the tumor surveillance of the host. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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9 pages, 641 KiB

Open AccessArticle

Pre-Treatment C-Reactive Protein Predicts Survival in Small Cell Lung Cancer Patients

by Anne Marie Stensvold, Ninna Aggerholm-Pedersen, Anne Winther-Larsen and Birgitte Sandfeld-Paulsen

Onco 2021, 1(2), 114-122; https://doi.org/10.3390/onco1020010 - 8 Nov 2021

Cited by 2 | Viewed by 3580

Abstract

Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based [...] Read more.

Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based on data from smaller studies. Data on SCLC patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and the clinical laboratory information system. CRP measurements were divided at the clinical cut-off value of 8 mg/L or 75 nmol/L) and stratified into quartiles. Cox proportional hazards model assessed the prognostic value of the CRP level. C-statistics further evaluated the biomarker’s prognostic value. In total, 923 patients were included. A pre-treatment CRP level above the clinical cut-off significantly correlated to inferior OS (adjusted hazard ratio (HR) = 1.25 (95% confidence interval (CI): 1.08–1.46). When divided into quartiles, a level-dependent correlation was observed with only the highest quartiles significantly associated with OS (3rd quartile: adjusted HR = 1.26 (95% CI: 1.03–1.55) 4th quartile: adjusted HR = 1.44 (95% CI: 1.17–1.77)). Adding CRP level to already well-established prognostic factors improved the prognostication of SCLC patients. In conclusion, high pre-treatment CRP level is an independent prognostic factor in SCLC patients. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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Review

Jump to: Research, Other

17 pages, 1423 KiB

Open AccessReview

The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia

by Margarida Silva, Diana Martins and Fernando Mendes

Onco 2022, 2(3), 164-180; https://doi.org/10.3390/onco2030011 - 11 Jul 2022

Cited by 1 | Viewed by 3037

Abstract

Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), [...] Read more.

Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, respectively. CTLA-4 blockage was a worthy therapeutic approach in relapsed hematologic malignancies, presenting long-lasting responses. The approach to AML and myelodysplastic syndrome patients with ICI before allogenic hematopoietic stem cell transplantation and the use of a graft-versus-host disease prophylaxis have shown improvement in the transplantation outcomes, and therefore AML treatment. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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20 pages, 1755 KiB

Open AccessReview

Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers

by Carolina Sousa, Beatriz Silva-Lima and Mafalda Videira

Onco 2022, 2(1), 36-55; https://doi.org/10.3390/onco2010004 - 25 Feb 2022

Cited by 4 | Viewed by 5192

Abstract

The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor [...] Read more.

The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor cell heterogeneity. Patient stratification based on the understanding of the relevant pathways, such as the PI3K/Akt axis crucial in EMT initiation, could favorably alter disease management. Significant clinical advantage could be expected when overexpressed Akt tyrosine kinase (Akt2) is addressed as a malignant biomarker to guide clinical management decisions, improving prognosis in lung cancer patients. Moreover, one should not miss the opportunity of using it as a druggable target aiming at the inhibition of the downstream complexity that underlies cell proliferation and survival, expression of stemness markers and drug resistance. The value of mTOR, as a downstream target of Akt, and the further activation of EMT transcription factors Twist, Snail and Zeb1 are revisited in this review. An in-depth state-of-the-art assessment provides evidence of its role in the mechanistic inhibition of epithelial markers, such as E-cadherin and miR-200, while inducing the expression of the mesenchymal ones, such as vimentin, N-cadherin, and miR-21. Lastly, evidence suggesting another transcription factor, FOXM1, as the link between the PI3K/Akt and Wnt/β-catenin pathways, prompting cell metabolism through the regulation of p70S6K, is analyzed. A more realistic approach is advised to address unmet clinical needs and support decision making at a clinical level. Taking into consideration several complex intracellular interactions might further improve patient stratification and result in better outcomes. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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12 pages, 262 KiB

Open AccessReview

Yttrium-90 Internal Radiation Therapy as Part of the Multimodality Treatment of Metastatic Colorectal Carcinoma

by Michael P. Del Rosario, Nadine Abi-Jaoudeh, May T. Cho, Zeljka Jutric and Farshid Dayyani

Onco 2021, 1(2), 207-218; https://doi.org/10.3390/onco1020015 - 11 Dec 2021

Viewed by 3320

Abstract

About 70% of patients with metastatic colorectal carcinoma (mCRC) have liver metastases. Hepatic failure accounts for most mCRC-related deaths. Therefore, controlling liver metastases may improve outcomes. A data overview of liver-directed treatment using yttrium-90 selective internal radiation therapy (SIRT) is provided as part [...] Read more.

About 70% of patients with metastatic colorectal carcinoma (mCRC) have liver metastases. Hepatic failure accounts for most mCRC-related deaths. Therefore, controlling liver metastases may improve outcomes. A data overview of liver-directed treatment using yttrium-90 selective internal radiation therapy (SIRT) is provided as part of a multimodality treatment. SIRT in mCRC is discussed, and the prognostic factors for patient selection are defined. Pooled analyses of three recent trials incorporating SIRT plus chemotherapy revealed subsets of patients with mCRC who might benefit from SIRT. A multidisciplinary treatment for most mCRC patients is proposed to achieve long-term survival in this cohort of patients. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

31 pages, 1680 KiB

Open AccessReview

Decoding the Oncogenic Signals from the Long Non-Coding RNAs

by Revathy Nadhan and Danny N. Dhanasekaran

Onco 2021, 1(2), 176-206; https://doi.org/10.3390/onco1020014 - 10 Dec 2021

Cited by 9 | Viewed by 4078

Abstract

Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a [...] Read more.

Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a clear understanding of the transcriptomic landscape of cancer cells. Recent innovative breakthroughs in high-throughput sequencing technologies have identified the oncogenic or tumor-suppressor role of several long non-coding RNAs (lncRNAs). LncRNAs have been characterized as regulating various signaling cascades which are involved in the pathobiology of cancer. They modulate cancer cell survival, proliferation, metabolism, invasive metastasis, stemness, and therapy-resistance through their interactions with specific sets of proteins, miRNAs and other non-coding RNAs, mRNAs, or DNAs in cells. By virtue of their ability to regulate multiple sets of genes and their cognate signaling pathways, lncRNAs are emerging as potential candidates for diagnostic, prognostic, and therapeutic targets. This review is focused on providing insight into the mechanisms by which different lncRNAs play a critical role in cancer growth, and their potential role in cancer diagnosis, prognosis, and therapy. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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18 pages, 609 KiB

Open AccessReview

Role of NK Cells in Cancer and Immunotherapy

by Paresh Vishwasrao, Susanta K. Hui, D. Lynne Smith and Vishal Khairnar

Onco 2021, 1(2), 158-175; https://doi.org/10.3390/onco1020013 - 3 Dec 2021

Cited by 5 | Viewed by 8027

Abstract

Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate [...] Read more.

Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate immune cells such as NK cells can also eliminate oncogenically transformed cells and regulate cells of the immune system. Considering NK cells as a live drug, numerous methods for the isolation and activation of NK cells have been shown to be clinically and therapeutically relevant. In such processes, various cytokines and antibodies present a source of stimulation of NK cells and enhance the efficacy of such treatments. The ex vivo expansion and activation of NK cells, along with genetic modification with CAR, enhance their antitumor activity. Recent preclinical studies have shown an antitumor effect through extracellular vesicles (EVs) derived from NK cells. Work with autologous NK cells has provided insights for clinical applications. In this review, we outline the recent advances of NK-cell-based immunotherapies, summarizing CAR-NK cells, BiKEs, and TriKEs as treatment options against cancer. This review also discusses the challenges of NK cell immunotherapy. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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34 pages, 1778 KiB

Open AccessReview

Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

by Ben Johnson, Kenneth Lee and Yuen Yee Cheng

Onco 2021, 1(2), 49-82; https://doi.org/10.3390/onco1020006 - 26 Sep 2021

Cited by 1 | Viewed by 4513

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are [...] Read more.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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Other

Jump to: Research, Review

5 pages, 935 KiB

Open AccessCommentary

The Role of Liquid Biopsy in the Diagnostic Testing Algorithm for Advanced Lung Cancer

by Aaron C. Tan

Onco 2022, 2(3), 181-185; https://doi.org/10.3390/onco2030012 - 14 Jul 2022

Cited by 4 | Viewed by 3682

Abstract

The discovery of therapeutically targetable oncogenic driver alterations has led to marked improvements in NSCLC outcomes. Targeted agents have been approved for an expanding list of biomarkers. Consequently, the accurate and timely identification of targetable alterations with diagnostic molecular profiling is crucial. The [...] Read more.

The discovery of therapeutically targetable oncogenic driver alterations has led to marked improvements in NSCLC outcomes. Targeted agents have been approved for an expanding list of biomarkers. Consequently, the accurate and timely identification of targetable alterations with diagnostic molecular profiling is crucial. The use of multiplexed tissue assays, such as next-generation sequencing (NGS), has increased significantly. However, significant limitations with tissue NGS remain, such as insufficient tissue, scheduling limitations, the need for repeat biopsies, and long turnaround times. Liquid biopsies, using plasma circulating tumor DNA (ctDNA), have the potential to overcome these issues, with simpler sample processing requirements, greater convenience, and better patient acceptability. In particular, an early liquid biopsy may allow patients access to highly effective therapies faster, allow better symptom control and quality of life, prevent rapid clinical deterioration, and reduce patient anxiety at diagnosis. More broadly, it may also allow for the more cost-effective delivery of healthcare to patients. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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11 pages, 285 KiB

Open AccessOpinion

Open Data to Support CANCER Science—A Bioinformatics Perspective on Glioma Research

by Fleur Jeanquartier, Claire Jean-Quartier, Sarah Stryeck and Andreas Holzinger

Onco 2021, 1(2), 219-229; https://doi.org/10.3390/onco1020016 - 13 Dec 2021

Cited by 1 | Viewed by 3335

Abstract

Supporting data sharing is paramount to making progress in cancer research. This includes the search for more precise targeted therapies and the search for novel biomarkers, through cluster and classification analysis, and extends to learning details in signal transduction pathways or intra- and [...] Read more.

Supporting data sharing is paramount to making progress in cancer research. This includes the search for more precise targeted therapies and the search for novel biomarkers, through cluster and classification analysis, and extends to learning details in signal transduction pathways or intra- and intercellular interactions in cancer, through network analysis and network simulation. Our work aims to support and promote the use of publicly available resources in cancer research and demonstrates artificial intelligence (AI) methods to find answers to detailed questions. For example, how targeted therapies can be developed based on precision medicine or how to investigate cell-level phenomena with the help of bioinformatical methods. In our paper, we illustrate the current state of the art with examples from glioma research, in particular, how open data can be used for cancer research in general, and point out several resources and tools that are readily available. Presently, cancer researchers are often not aware of these important resources. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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6 pages, 580 KiB

Open AccessCommentary

Tumor-Agnostic Biomarkers: Heed Caution, and Why Cell of Origin Still Matters

by Aaron C. Tan

Onco 2021, 1(2), 95-100; https://doi.org/10.3390/onco1020008 - 27 Oct 2021

Cited by 1 | Viewed by 4774

Abstract

Since the very beginnings of cancer therapy with chemotherapy, tumors have been treated according to the organ or tissue of origin. The advent of precision medicine however, has recently led to growing promise for tumor-agnostic biomarkers for targeted therapies and immunotherapies, such as [...] Read more.

Since the very beginnings of cancer therapy with chemotherapy, tumors have been treated according to the organ or tissue of origin. The advent of precision medicine however, has recently led to growing promise for tumor-agnostic biomarkers for targeted therapies and immunotherapies, such as NTRK fusions. Despite this, prominent examples such as BRAF V600E mutations in melanoma compared to colorectal cancer, in which the site of tumor origin dramatically influences the efficacy of targeted therapies, heeds caution against disregarding the importance of cell of origin. Indeed, another illustrative example, is the almost complete absence outside of cancers originating from the lung of the classical activating EGFR mutations—exon 19 deletions and exon 21 L858R mutations. Consequently, an understanding of lineage dependency and lineage-survival oncogenes may still offer significant mechanistic insights into the malignant transformation of tumors to ultimately identify further therapeutic vulnerabilities. Full article

(This article belongs to the Special Issue Feature Papers in Onco)

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