Cancer Research

Oncotarget

Oncotarget published this research perspective on May 19, 2023 in Volume 14, entitled, “Targeting the Src N-terminal regulatory element in cancer" by researchers from Biomolecular NMR Lab, Departament de Química Inorgànica i Orgànica, Universitat de Barcelona (UB), Barcelona 08028, Spain; Departament de Ciències Bàsiques, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès 08195, Spain.

DOI - https://doi.org/10.18632/oncotarget.28434

Correspondence to - Miquel Pons - mpons@ub.edu

Abstract

The signaling pathways displayed by cancer cells are often composed by the same components than the physiological ones, yet the overall result is a pathological deregulation. The non-receptor protein tyrosine kinase Src is a good example. Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity. Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells.

The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, we discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets.

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Keywords - Src family kinases, intrinsically disordered proteins, SNRE, cell-type selective drugs, drug resistance

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Targeting the Src N-Terminal Regulatory Element in Cancer

Oncotarget published this trending research paper on May 26, 2023 in Volume 14, entitled, “Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC)" by researchers from the Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, Division of Hematology and Oncology, Hotel Dieu de France University Hospital, Beirut, Lebanon.

DOI - https://doi.org/10.18632/oncotarget.28444

Correspondence to - Fadi El Karak - Felkarak@yahoo.com

Abstract

Background: Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy.

Methods: This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians’ clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC.

Results: A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months.

Conclusion: New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.

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Keywords - chemotherapy, immunotherapy, non-small cell lung cancer

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Value of Chemotherapy Post Immunotherapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)

Oncotarget published this research paper on May 26, 2023 in Volume 14, entitled, “Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression" by researchers from the Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, India; Department of Orthodontics and Dentofacial Orthopedics, ITS Dental College, Hospital and Research Centre, Greater Noida, Delhi-NCR, India; Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; Department of Medical Laboratory, College of Applied Medical Sciences, Qassim University, Qassim, Saudi Arabia; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Surgical Oncology, BRA- IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Department of Neurology, Henry Ford Health System, Detroit, MI; School of Biotechnology, Jawahar Lal Nehru University, New Delhi, India.

DOI - https://doi.org/10.18632/oncotarget.28442

Correspondence to - Mohammad Salman Akhtar - mdsalmanakhtar@yahoo.com, milyas@bu.edu.sa

Abstract

Introduction: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases.

Materials and Methods: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation polymorphisms (PCR-SSCP) and automated DNA sequencing and by immunohistochemistry for BORIS protein expression were performed. The observed findings were correlated with several clinicopathological parameters to find out the clinical relevance of associations.

Results: Of all the cases 16.12% (25/155) showed mutations in the BORIS gene. The observed mutations present on codon 329 are missense, leading to Val> Ile (G>A) change on exon 5 of the BORIS gene. A significant association was observed between mutations of the BORIS gene and some clinicopathological features like nodal status (p = 0.013), estrogen receptor (ER) expression (p = 0.008), progesterone receptor (PR) expression (p = 0.039), clinical stage (p = 0.010) and menopausal status (p = 0.023). The protein expression analysis showed 20.64% (32/155) samples showing low or no expression (+), 34.19% (53/155) with moderate expression (++), and 45.17% (70/155) showing high expression (+++) of BORIS protein. A significant association was observed between the expression of BORIS protein and clinicopathological features like clinical stage (p = 0.013), nodal status (p = 0.049), ER expression (p = 0.039), and PR expression (p = 0.027). When mutation and protein expression were correlated in combination with clinicopathological parameters a significant association was observed in the category of high (+++) level of BORIS protein expression (p = 0.017).

Conclusion: The BORIS mutations and high protein expression occur frequently in carcinoma of the breast suggesting their association with the onset and progression of breast carcinoma. Further, the BORIS has the potential to be used as a biomarker.

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Keywords - BORIS, breast cancer, mutation, transcription factor, PCR-SSCP

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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BORIS Gene Mutation and Expression: Link to Breast Cancer Progression

Aging (Aging-US)

The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. 

This charity bike ride, based out of Buffalo, New York, has brought people together for 27 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure. This year's Ride will take place on Saturday, June 24 from the University at Buffalo, North Campus. 

Impact Journals (Aging's publisher) has been a part of the Ride for Roswell since 2018. Impact Journals sponsors captain Sergei Kurenov’s peloton, Team Open Access (named after open-source online medical journals, such as Aging, Oncotarget, Genes & Cancer, and Oncoscience).

Sergei - who has been riding in the event since 2016 - works at Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment.

“Roswell Park Comprehensive Cancer Center is dedicated to providing a high level of care for cancer patients,” Sergei said. “By contributing to the Ride for Roswell, we are helping our patients to fight this most dangerous disease.”

There is still time to join Team Open Access and the 2023 Ride for Roswell. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives. 

“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support,” Sergei said. “Together, we can make a difference!”

Team Open Access page - https://give.roswellpark.org/site/TR/SpecialEvents/General?px=1045122&pg=personal&fr_id=1830

Ride for Roswell - https://www.rideforroswell.org/

Keywords - aging, cancer research, open access, Impact Journals, science, oncology, research, fundraising, bicycling, Ride for Roswell, Roswell Park Comprehensive Cancer Center

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Impact Journals Sponsors Team Open Access in 2023 Ride for Roswell

The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. 

This charity bike ride, based out of Buffalo, New York, has brought people together for 27 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure. This year's Ride will take place on Saturday, June 24 from the University at Buffalo, North Campus. 

Impact Journals (Oncotarget's publisher) has been a part of the Ride for Roswell since 2018. Impact Journals sponsors captain Sergei Kurenov’s peloton, Team Open Access (named after open-source online medical journals, such as Oncotarget, Aging, Genes & Cancer, and Oncoscience).

Sergei - who has been riding in the event since 2016 - works at Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment.

“Roswell Park Comprehensive Cancer Center is dedicated to providing a high level of care for cancer patients,” Sergei said. “By contributing to the Ride for Roswell, we are helping our patients to fight this most dangerous disease.”

There is still time to join Team Open Access and the 2023 Ride for Roswell. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives. 

“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support,” Sergei said. “Together, we can make a difference!”

Team Open Access page - https://give.roswellpark.org/site/TR/SpecialEvents/General?px=1045122&pg=personal&fr_id=1830

Ride for Roswell - https://www.rideforroswell.org/

Keywords - cancer research, open access, Impact Journals, science, oncology, research, fundraising, bicycling, Ride for Roswell, Roswell Park Comprehensive Cancer Center

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Thermo Fisher Scientific | qPCR

Reliable testing and diagnostics on a large scale is more important than ever. Dr. Gustav Quade shares how the QuantStudio™ 7 Pro Dx instrument, Diomni™ software, and qPCR products revolutionized their testing capabilities and their impact on patients' lives.

Learn more at https://www.thermofisher.com/us/en/home/clinical/clinical-genomics/molecular-diagnostics-solutions.html

Contact a support specialist: https://www.thermofisher.com/us/en/home/global/forms/life-science/quantstudio-dx-quote.html

For In Vitro Diagnostics use.


Automated Applied Biosystems qPCR tools for MDx development

Dr. Lauren Bates uses qPCR for pathogen identification and depends on Applied Biosystems QuantStudio Real-Time PCR systems and reagents to achieve optimal results with quick response times. Learn how Thermo Fisher Scientific empowers Dr. Lauren Bates and her team to take charge of disease identification and improve the lives of those we love. 

Learn more - https://www.thermofisher.com/us/en/home/clinical/clinical-genomics/molecular-diagnostics-solutions.html

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For In Vitro Diagnostic Use.

qPCR for pathogen identification with Applied Biosystems QuantStudio Real-Time PCR systems

Oncotarget published this research paper on May 26, 2023 in Volume 14, entitled, “Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment" by researchers from the Department of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA; Department of Dermatology, Clinic Landstrasse Vienna, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; School of Medicine, University of California San Francisco, San Francisco, CA.

DOI - https://doi.org/10.18632/oncotarget.28447

Correspondence to - Valentin Feichtenschlager - valentin.feichtenschlager@ucsf.edu

Abstract

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK and ERK in melanoma is largely unknown. We demonstrate the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin. Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.

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Keywords - MALAT1, MAPK-pathway, BRAF, melanoma, antisense oligonucleotides

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Deconstructing the Role of MALAT1 in MAPK-Signaling in Melanoma

Oncotarget published this trending research paper on May 19, 2023 in Volume 14, entitled, “Role of creatine shuttle in colorectal cancer cells" by researchers from the Department of Molecular Pathology, Nara Medical University, Kashihara, Nara 634-8521, Japan; Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India; Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China.

DOI - https://doi.org/10.18632/oncotarget.28436

Correspondence to - Hiroki Kuniyasu -  cooninh@zb4.so-net.ne.jp, and Rina Fujiwara-Tani - rina_fuji@naramed-u.ac.jp

Abstract

The creatine shuttle translocates the energy generated by oxidative phosphorylation to the cytoplasm via mitochondrial creatine kinase (MTCK) and creatine kinase B (CKB) in the cytoplasm. It is not apparent how the creatine shuttle is related to cancer. Here, we analyzed the expression and function of CKB and MTCK in colorectal cancer (CRC) and investigated the role of the creatine shuttle in CRC. Compared with normal mucosa, 184 CRC tissues had higher levels of CKB and MTCK, and these levels were associated with histological grade, tumor invasion, and distant metastasis. CK inhibitor dinitrofluorobenzene (DNFB) on CRC cell lines HT29 and CT26 inhibited cell proliferation and stemness to less than 2/3 and 1/20 of their control levels, respectively. In this treatment, the production of reactive oxygen species increased, mitochondrial respiration decreased, and mitochondrial volume and membrane potential decreased. In a syngeneic BALB/c mouse model using CT26 cells pretreated with DNFB, peritoneal metastasis was suppressed to 70%. Phosphorylation of EGFR, AKT, and ERK1/2 was inhibited in DNFB-treated tumors. High ATP concentrations prevented EGFR phosphorylation in HT29 cells following DNFB treatment, CKB or MTCK knockdown, and cyclocreatine administration. Despite not being immunoprecipitated, CKB and EGFR were brought closer together by EGF stimulation. These findings imply that blocking the creatine shuttle decreases the energy supply, suppresses oxidative phosphorylation, and blocks ATP delivery to phosphorylation signals, preventing signal transduction. These findings highlight the critical role of the creatine shuttle in cancer cells and suggest a potential new cancer treatment target.

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Keywords - creatine kinase B, mitochondrial creatine kinase, ATP metabolism, phosphorylation signal, stemness

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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