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Oncotarget
By Oncotarget PodcastScience
Oncotarget episodes
- The Evolution of Metastatic Cancer: Mechanisms and DriversListen to a blog summary of an editorial published in Oncotarget on March 21, 2023, entitled, “Therapy drives genomic evolution in metastatic cancer._________________________________________________There are several theories that attempt to explain the genesis of cancer. One prominent theory is the genetic theory—proposing that cancer may arise from the accumulation of genetic mutations that alter the normal functioning of cells. These mutations can drive the formation of tumors, which can then spread to other parts of the body in a process known as metastasis. Metastatic cancer is often difficult to treat because it has evolved to become resistant to standard therapies.“It is generally accepted that development of cancer is a slow process, likely spanning decades during which the developing neoplastic cells sequentially acquire genomic alterations that will eventually give rise to the primary tumor [1].”In a new editorial, researchers Ditte S. Christensen and Nicolai J. Birkbak from Aarhus University discuss mechanisms of genomic evolution in metastatic cancer, how therapy can drive it and the implications for developing new treatments. Their editorial paper was published in Oncotarget on March 21, 2023, entitled, “Therapy drives genomic evolution in metastatic cancer.”Full blog - https://www.oncotarget.org/2023/04/14/the-evolution-of-metastatic-cancer-mechanisms-and-drivers/Paper DOI - https://doi.org/10.18632/oncotarget.28379 (PDF)Correspondence to - Nicolai J. Birkbak - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28379Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer evolution, metastatic cancer mutations, treatment-induced mutations, GENIEAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209578 min
- Cancer Prevention with RapamycinA new research perspective was published in Oncotarget's Volume 14 on April 14, 2023, entitled, “Cancer prevention with rapamycin.”The mTOR (Target of Rapamycin) pathway is involved in both cancer and aging. Furthermore, common cancers are age-related diseases, and their incidence increases exponentially with age. In his new research perspective, Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses rapamycin and other rapalogs and their potential to delay cancer by targeting pre-cancerous cells and slowing down organismal aging.“Rapamycin (sirolimus) and other rapalogs (everolimus) are anti-cancer and anti-aging drugs, which delay cancer by directly targeting pre-cancerous cells and, indirectly, by slowing down organism aging.”Cancer is an age-related disease and, figuratively, by slowing down time (and aging), rapamycin may delay cancer. In several dozen murine models, rapamycin robustly and reproducibly prevents cancer.Rapamycin slows cell proliferation and tumor progression, thus delaying the onset of cancer in carcinogen-treated, genetically cancer-prone and normal mice. Data on the use of rapamycin and everolimus in organ-transplant patients are consistent with their cancer-preventive effects.Treatment with rapamycin was proposed to prevent lung cancer in smokers and former smokers. Clinical trials in high-risk populations are warranted.“Currently, an increasing number of healthy people use rapamycin off-label to slow down aging. Perhaps in ten or twenty years from now, data will accumulate for retrospective analysis of cancer-prevention with rapamycin in humans.”DOI: https://doi.org/10.18632/oncotarget.28410Correspondence to: Mikhail V. Blagosklonny - [email protected], [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28410Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - chemoprevention, lung, rapamycin, aging, cancerAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209573 min
- Riluzole and Sorafenib in Patients With Advanced Solid Tumors: A Phase I TrialA new research paper was published in Oncotarget's Volume 14 on April 10, 2023, entitled, “A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850.”Overexpression of metabotropic glutamate receptor 1 (GRM1) has been implicated in the pathogenesis of multiple cancers. Riluzole, an inhibitor of glutamate release, showed synergistic antitumor activity in combination with the multi-kinase inhibitor sorafenib in preclinical models.In a new phase I trial, researchers Kristen R. Spencer, Daniella E. Portal, Joseph Aisner, Mark N. Stein, Jyoti Malhotra, Weichung Shih, Nancy Chan, Ann W. Silk, Shridar Ganesan, Susan Goodin, Murugesan Gounder, Hongxia Lin, Jiadong Li, Robert Cerchio, Christina Marinaro, Suzie Chen, and Janice M. Mehnert from Rutgers University, Dana-Farber Cancer Institute, and the Perlmutter Cancer Center of NYU Langone Health identified the toxicity profile, dose-limiting toxicities, maximum tolerated dose (MTD), and pharmacokinetic and pharmacodynamic properties of riluzole combined with sorafenib in patients with advanced cancers.“Riluzole functions as an inhibitor of GRM1 signaling through antagonism of glutamate release, and sorafenib is a multi-kinase inhibitor targeting both the MAPK and PI3K/AKT pathways through the inhibition of RAF1, ARAF and, to a lesser extent BRAF, as well as a set of tyrosine kinases including VEGFR. Our phase I study determined the tolerable dose of this combination and investigated its biologic effects.”Patients with refractory solid tumors were enrolled utilizing a 3+3 dose-escalation design. Riluzole was given at 100 mg PO BID in combination with sorafenib, beginning at 200 mg PO daily and escalating in 200 mg increments per level in 28-day cycles. Restaging evaluations were performed every 2 cycles. In total, 35 patients were enrolled over 4 dose levels.The MTD was declared at dose level 3 (riluzole: 100 mg PO BID; sorafenib: 400 mg AM/200 mg PM). Pharmacokinetic analyses did not reveal definitive evidence of drug-drug interactions. Consistent decreases in phospho-forms of ERK and AKT in tumor tissue analyses with accompanying decrease in GRM1 expression and increase in pro-apoptotic BIM suggest target engagement by the combination. Best responses included a partial response in 1 (2.9%) patient with pancreatic acinar cell carcinoma with a KANK4-RAF1 fusion, and stable disease in 11 (36%) patients.“Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.”DOI: https://doi.org/10.18632/oncotarget.28403Correspondence to: Janice M. Mehnert - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28403Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - GRM1, riluzole, sorafenib, phase I, clinical trialAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/4 min
- Crosstalk Between Triple Negative Breast Cancer and MicroenvironmentA new review paper was published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Crosstalk between triple negative breast cancer and microenvironment.”Although many advances have been made in the treatment of breast cancer, for triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but effective therapies are currently not available.In their new review, researchers Karly Smrekar, Artem Belyakov and Kideok Jin from Albany College of Pharmacy and Health Science discuss recent progress in our understanding of TNBC, advancements in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC.“Technological advancements such as genomics and epigenomics have provided us with vast insight about the complexity of breast cancer. However, one thing has remained the same, the need for the evaluation of three markers. These three markers; the expression of estrogen, progesterone, and HER2, are all molecular targets for treatment regimens, and are relied on by clinicians [1]. Chemotherapy is the staple treatment for TNBC patients. However, they lack the expression of three key therapeutic markers. The lack of therapeutic markers leads to poorer outcomes in TNBC.”DOI: https://doi.org/10.18632/oncotarget.28397Correspondence to: Kideok Jin - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28397Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - triple negative breast cancer, tumor microenvironment, current therapyAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209573 min
- Cancer-Associated Fibroblasts: Challenges and OpportunitiesA new editorial perspective was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Cancer-associated fibroblasts: challenges and opportunities.”Cancer-associated fibroblasts (CAFs) are a type of cell that plays a key role in the tumor microenvironment. While these cells have been extensively studied, their precise role in cancer development and progression is still not fully understood.In this new editorial perspective, researchers Hossein Tavana and Gary D. Luker from The University of Akron and the University of Michigan provide a comprehensive overview of CAFs, including the origins, characteristics, heterogeneity, and functions of CAFs, as well as CAFs in the detection and treatment of cancer.The authors suggest that a deeper understanding of cancer-associated fibroblasts is crucial for the development of effective cancer therapies. They note that these cells are involved in a variety of important processes, including tumor growth, angiogenesis and immune evasion. However, targeting cancer-associated fibroblasts has proven to be a challenging task, in part because of their complex and multifaceted nature.Despite these challenges, the researchers are optimistic about the future of research into CAFs. They note a number of studies targeting cancer-associated fibroblasts in emerging therapies. The authors conclude by emphasizing that a deeper understanding of cancer-associated fibroblasts and the tumor microenvironment could ultimately lead to the development of personalized therapies that are tailored to the unique characteristics of each patient's cancer.“Delineating cross-talk of CAFs with cancer cells and other stromal cells, uncovering the role of CAFs in resistance to chemotherapies and immunotherapies, addressing challenges associated with CAFs heterogeneity to develop CAFs subtype-targeted therapies in the context of specific tumor types, and addressing the potential toxicity of such therapies especially when combined with other treatments will expedite the ongoing efforts for the translation of therapies against CAFs.”Editorial perspective: DOI: https://doi.org/10.18632/oncotarget.28385Correspondence to: Hossein Tavana - [email protected]Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - fibroblasts, cancer-associated fibroblasts, tumor microenvironment, therapeutic targetingAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209573 min
- Impact of Cortactin in Cancer ProgressionA new editorial paper was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Impact of cortactin in cancer progression on Wnt5a/ROR1 signaling pathway.”In this editorial, researchers Kamrul Hasan and Thomas J. Kipps from the University of California discuss cortactin—an intracellular cytoskeletal protein that can undergo tyrosine phosphorylation upon external stimulation and promote polymerization and the assembly of the actin filament that is required for cell migration. Upon stimulation, cortactin binds and activates actin related protein Arp2/3 complex, a de novo actin nucleator that can induce F (filamentous)-actin polymerization [1, 2].Cortactin (also known as EMS1 or CTTN) is expressed broadly in a variety of cancers, for which it plays an apparent role in cellular protrusions, which include lamellipodia and filopodia formation to promote migration and metastasis. Moreover, cortactin is expressed in (i) primary chronic lymphocytic leukemia (CLL) and primary breast-cancer cells, (ii) at least 15% of metastatic breast carcinomas, and (iii) CLL or breast-cancer cell-lines [3, 4]. In structure, cortactin contains a SH3 domain that allows it to bind characteristic motifs (-P-X-X-P-), which can be found in the proline-rich-domains (PRD) of other proteins, including receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) [1, 3, 4].“We have found (as have other investigators) that ROR1 is expressed by a variety of human cancers, which include CLL and breast cancer, suggesting that ROR1 may play a role in cancer pathogenesis [3–5].”Editorial paper: DOI: https://doi.org/10.18632/oncotarget.28386Correspondence to: Thomas J. Kipps - [email protected]Keywords: cortactin, Wnt5a, ROR1, migration, metastasisSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209573 min
- Oncotarget at AACR Annual Meeting 2023Impact Journals (Oncotarget's publisher) will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2023 from April 14-19 at the Orange County Convention Center in Orlando, Florida. This year, the AACR meeting theme is: “Advancing the Frontiers of Cancer Science and Medicine.”Impact Journals publishes scholarly journals in the biomedical sciences with a focus on all areas of cancer and aging research. Oncotarget is one of the most prominent journals published by Impact Journals. Oncotarget is indexed/archived on MEDLINE, PMC and PubMed.Visit booth No. 2642 at the AACR Annual Meeting 2023 to connect with members of the Oncotarget team.Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cancer research, aacr, aacr23, aacr2023, annual meeting, meeting, conference, press, press release, announcementAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209572 min
- Targeting Pre-Leukemic Cells: New Hope for Preventing Childhood B-ALLListen to a blog summary of an editorial in Volume 14, entitled, “Proof-of-principle: targeted childhood leukemia prevention.”___________________________________________Childhood leukemia is a devastating disease that affects thousands of children every year. Despite significant advancements in the field of pediatric oncology, childhood leukemia remains a major cause of morbidity and mortality in children, with B-cell acute lymphoblastic leukemia (B-ALL) being the most common form.Some cases of childhood B-ALL arise from congenital mutations that lead to a silent population of pre-leukemic cells. These cells at some point are triggered by a catalyst (possibly by delayed exposure to a common infection), acquire additional genetic mutations and ultimately develop into B-ALL. However, researchers have yet to fully understand how to target these pre-leukemic cells to prevent B-ALL.In a new editorial paper, researchers César Cobaleda, Manuel Ramírez-Orellana, Carolina Vicente-Dueñas, Andreas Weiss, Kim E. Nichols, and Isidro Sánchez-García from Universidad Autónoma de Madrid discuss a novel method of targeting pre-leukemic cells in practice. On March 11, 2023, the team published their editorial in Oncotarget, entitled, “Proof-of-principle: targeted childhood leukemia prevention.”“[…] one would have to find a way to specifically target these preleukemic cells. Recently, a mouse model recapitulating the phenotype of a leukemia-predisposition syndrome has allowed us to carry out a proof-of-principle experiment to achieve this very goal.”Full blog - https://www.oncotarget.org/2023/03/31/targeting-pre-leukemic-cells-new-hope-for-preventing-childhood-b-all/Paper DOI - https://doi.org/10.18632/oncotarget.28371Correspondence to - César Cobaleda - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/deta...Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - leukemia, infection, murine models, genetic susceptibility, preventionAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209578 min
- Downregulation of Angulin-1/LSR Induces Malignancy in Lung AdenocarcinomaA new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.”Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR).In the present study, researchers Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, and Takashi Kojima from Sapporo Medical University School of Medicine examined expression of claudin-2 in the lung adenocarcinoma tissues and found it was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed.“We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells.”The researchers found that the EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells.The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.“In conclusion, AG1478 and EW-7197 demonstrated potent in vitro anti-lung adenocarcinoma therapeutic activities via LSR/CLDN-2 and the cell metabolism. The use of both AG1478 and EW-7197 may provide a clinical therapeutic approach for lung adenocarcinoma caused by loss of angulin-1/LSR.”Full research paper: DOI: https://doi.org/10.18632/oncotarget.27728Correspondence to: Takashi Kojima - [email protected]Keywords: angulin-1/LSR, claudin-2, cell metabolism, malignancy, lung adenocarcinomaAbout OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209575 min
- Polyisoprenylated Cysteinyl Amide Inhibitors Deplete G-Proteins in Cancer CellsA new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer cell lines.”Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. It is hypothesized that PCAIs work as anticancer agents by disrupting polyisoprenylation-dependent functional interactions of the G-Proteins.In their new study, researchers Nada Tawfeeq, Jassy Mary S. Lazarte, Yonghao Jin, Matthew D. Gregory, and Nazarius S. Lamango from Florida A&M University College of Pharmacy Pharmaceutical Sciences and Imam Abdulrahman bin Faisal University tested this hypothesis by determining the effect of the PCAIs on the levels of RAS and related monomeric G-proteins.“To investigate the hypothesized anticancer mechanisms of the PCAIs through disruption of G-protein function, we checked the effects of the PCAIs on the G-protein levels in lung cancer (A549 and NCI-H1299) and breast cancer (MDA-MB-231 and MDA-MB-468) cell lines.”Following 48 hours of exposure, they found significant decreases in the levels of KRAS, RHOA, RAC1, and CDC42 ranging within 20–66% after NSL-YHJ-2-27 (5 μM) treatment in all four cell lines tested, A549, NCI-H1299, MDA-MB-231, and MDA-MB-468. However, no significant difference was observed on the G-protein, RAB5A. Interestingly, 38 and 44% decreases in the levels of the farnesylated and acylated NRAS were observed in the two breast cancer cell lines, MDA-MB-231, and MDA-MB-468, respectively, while HRAS levels showed a 36% decrease only in MDA-MB-468 cells.Moreover, after PCAIs treatment, migration, and invasion of A549 cells were inhibited by 72 and 70%, respectively while the levels of vinculin and fascin dropped by 33 and 43%, respectively. Their results show that PCAIs deplete the protein levels of some significant G-proteins which are known to be involved in the migration and invasion of cells (i.e., metastasis) such as RAC1, RHOA, and CDC42. These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins.“The initial findings presented here indicate how PCAIs can be used as potent agents in developing new anticancer therapeutics, therefore, more extensive studies need to be done to elucidate on its potency. Although we cannot conclusively explain the exact mechanism of action of PCAIs on how they affect the levels of some G-proteins yet, but we can say that these PCAIs have the ability to affect the progression of cancer.”Research paper: DOI: https://doi.org/10.18632/oncotarget.28390Correspondence to: Nazarius S. Lamango - [email protected]Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords: PCAIs, G-proteins, KRAS, RHOA, RAC1About OncotargetOncotarget 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.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209575 min
About Oncotarget
From the publisher's feed
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.
Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.
Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/