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Cells
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Recent Advances in Cancer Therapy
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Recent Advances in Cancer Therapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 22134

Special Issue Editor

Dr. Anand Singh

E-Mail Website
Guest Editor
Center for Cancer Research, National Cancer Institute, NIH Bethesda, MD 20892-1201, USA
Interests: cancer; cell signaling; epigenetics; microRNA; targeted therapy; carcinogenesis; apoptosis

Special Issue Information

Dear Colleagues,

Cancer remains one of the leading causes of death worldwide. The major contributing factors include the molecular changes or mutations in the genetic material of the cells due to various environmental stresses or inherited genetic disorders. Conventional chemotherapy has been an effective treatment for cancer, but its success is limited due to off-target toxicity and the development of drug-resistant tumor cells. Over the past several years, immunotherapy and targeted and gene therapies have been gaining attention due to their specificity towards cancer cells. These therapies, based on molecular changes in tumor cells, specifically inhibit biologic signaling pathways that drive tumor growth and/or specific oncogenes or proteins to induce apoptosis in cancer cells and activation of the immune system, which recognizes and destroys cancer cells, while minimizing off-target toxicity.

Immunotherapy, which uses the immune system of patients against cancer, is emerging as a potential treatment for many different types of cancer. Immunotherapies, such as chimeric antigen receptor T-cell therapy (CART), T-cell receptor therapy (TCR), and tumor-infiltrating lymphocytes (TIL) are being tested in clinical trials of patients who have acute lymphoblastic leukemia (ALL), large B-cell lymphoma, sarcoma, or colorectal, kidney, ovarian, or skin cancers, such as melanoma, and early results are promising. In cancer patients, targeted therapies, such as small molecule inhibitors and monoclonal antibodies alone or in combination with traditional drugs, have shown significant improvement in survival rate with decreased side effects.

MicroRNA (miRNA)-based gene therapy has great therapeutic potential in cancer treatment due to its differential expression profile. MicroRNAs are 21–23 nucleotides long—a class of non-coding RNA molecules that regulate gene expression in various biological processes. The expression of miRNAs is tissue and disease specific. A unique feature of miRNA-based regulation is the ability of individual miRNAs to regulate multiple genes simultaneously, which, in turn, regulates multiple signaling pathways. The expression of many miRNAs is altered in cancers, and these alterations are specific to cancer types. Targeting of altered miRNA pathways in cancer provides a new and potential candidate for therapeutic intervention of different cancers. Recently, a few miRNA-based cancer therapies have demonstrated therapeutic potential in preclinical models and have entered into the clinical stage. The aim of this Special Issue is to cover recent advances in the field of cancer immunotherapy, targeted cancer therapy, and miRNA-based cancer therapy. We would like to put emphasis on the molecular mechanism that is associated with the pathogenesis of cancer and that can be targeted for therapeutic purposes. We invite contributions in the form of original research articles and reviews.

We look forward to your contributions.

Dr. Anand Singh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer
  • Immunotherapy
  • Targeted therapy
  • MicroRNA
  • Small molecule inhibitors
  • Cell signaling
  • Apoptosis

Published Papers (6 papers)

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Research

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15 pages, 4984 KiB  
Article
Augmented Antitumor Effect of Unripe Rubus coreanus Miquel Combined with Oxaliplatin in a Humanized PD-1/PD-L1 Knock-In Colorectal Cancer Mouse Model
by Eun-Ji Lee, Ju-Hye Yang, Jang-Gi Choi and Hwan-Suck Chung
Cells 2022, 11(18), 2876; https://doi.org/10.3390/cells11182876 - 14 Sep 2022
Cited by 2 | Viewed by 2452
Abstract
Immune checkpoint inhibitors (ICIs) have been shown to be extraordinarily effective in patients with colorectal cancer (CRC). However, the current ICIs still have adverse effects and limited efficacy of ICI monotherapy. We used a natural product to overcome the vulnerability of ICIs and [...] Read more.
Immune checkpoint inhibitors (ICIs) have been shown to be extraordinarily effective in patients with colorectal cancer (CRC). However, the current ICIs still have adverse effects and limited efficacy of ICI monotherapy. We used a natural product to overcome the vulnerability of ICIs and tried a combination therapy with oxaliplatin to enhance the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade anticancer effect. In the present study, we evaluated the T cell-mediated antitumor immunity with Unripe Rubus coreanus Miquel extract (RCE), which exerts anticancer properties via PD-1/PD-L1 blockade, combined with oxaliplatin in a co-culture cell model and allograft tumor humanized PD-1 mice. We found that RCE plus oxaliplatin apparently activates hPD-1 tumor-infiltrating CD8+ T cells, resulting in elevations of released interleukin-2 (IL-2) and granzyme B (GrB), and kills hPD-L1 MC38 CRC cells. RCE plus oxaliplatin considerably reduced tumor growth in humanized PD-1/PD-L1-expressing mouse MC38 CRC allograft. Moreover, RCE plus oxaliplatin remarkably increased the infiltration of CD8+ T cells in tumor tissues, as well as increasingly produced GrB of tumor-infiltrating CD8+ T cells in the tumor microenvironment. Our study delineated combination therapy with RCE as a PD-1/PD-L1 blockade and oxaliplatin to improve the response to immune checkpoint blockade therapy in conjunction with standard chemotherapy regimens in CRC. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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21 pages, 61524 KiB  
Article
The AGEs/RAGE Transduction Signaling Prompts IL-8/CXCR1/2-Mediated Interaction between Cancer-Associated Fibroblasts (CAFs) and Breast Cancer Cells
by Maria Francesca Santolla, Marianna Talia, Francesca Cirillo, Domenica Scordamaglia, Salvatore De Rosis, Asia Spinelli, Anna Maria Miglietta, Bruno Nardo, Gianfranco Filippelli, Ernestina Marianna De Francesco, Antonino Belfiore, Rosamaria Lappano and Marcello Maggiolini
Cells 2022, 11(15), 2402; https://doi.org/10.3390/cells11152402 - 04 Aug 2022
Cited by 8 | Viewed by 2525
Abstract
Advanced glycation end products (AGEs) and the cognate receptor, named RAGE, are involved in metabolic disorders characterized by hyperglycemia, type 2 diabetes mellitus (T2DM) and obesity. Moreover, the AGEs/RAGE transduction pathway prompts a dysfunctional interaction between breast cancer cells and tumor stroma toward [...] Read more.
Advanced glycation end products (AGEs) and the cognate receptor, named RAGE, are involved in metabolic disorders characterized by hyperglycemia, type 2 diabetes mellitus (T2DM) and obesity. Moreover, the AGEs/RAGE transduction pathway prompts a dysfunctional interaction between breast cancer cells and tumor stroma toward the acquisition of malignant features. However, the action of the AGEs/RAGE axis in the main players of the tumor microenvironment, named breast cancer-associated fibroblasts (CAFs), remains to be fully explored. In the present study, by chemokine array, we first assessed that interleukin-8 (IL-8) is the most up-regulated pro-inflammatory chemokine upon AGEs/RAGE activation in primary CAFs, obtained from breast tumors. Thereafter, we ascertained that the AGEs/RAGE signaling promotes a network cascade in CAFs, leading to the c-Fos-dependent regulation of IL-8. Next, using a conditioned medium from AGEs-exposed CAFs, we determined that IL-8/CXCR1/2 paracrine activation induces the acquisition of migratory and invasive features in MDA-MB-231 breast cancer cells. Altogether, our data provide new insights on the involvement of IL-8 in the AGEs/RAGE transduction pathway among the intricate connections linking breast cancer cells to the surrounding stroma. Hence, our findings may pave the way for further investigations to define the role of IL-8 as useful target for the better management of breast cancer patients exhibiting metabolic disorders. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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19 pages, 8300 KiB  
Article
Pimozide Suppresses the Growth of Brain Tumors by Targeting STAT3-Mediated Autophagy
by Alok Ranjan, Itishree Kaushik and Sanjay K. Srivastava
Cells 2020, 9(9), 2141; https://doi.org/10.3390/cells9092141 - 22 Sep 2020
Cited by 24 | Viewed by 3463
Abstract
Brain tumors are considered as one of the most aggressive and incurable forms of cancer. The majority of the patients with brain tumors have a median survival rate of 12%. Brain tumors are lethal despite the availability of advanced treatment options such as [...] Read more.
Brain tumors are considered as one of the most aggressive and incurable forms of cancer. The majority of the patients with brain tumors have a median survival rate of 12%. Brain tumors are lethal despite the availability of advanced treatment options such as surgical removal, chemotherapy, and radiotherapy. In this study, we have evaluated the anti-cancer effects of pimozide, which is a neuroleptic drug used for the treatment of schizophrenia and chronic psychosis. Pimozide significantly reduced the proliferation of U-87MG, Daoy, GBM 28, and U-251MG brain cancer cell lines by inducing apoptosis with IC50 (Inhibitory concentration 50) ranging from 12 to 16 μM after 48 h of treatment. Our Western blotting analysis indicated that pimozide suppressed the phosphorylation of STAT3 at Tyr705 and Src at Tyr416, and it inhibited the expression of anti-apoptotic markers c-Myc, Mcl-1, and Bcl-2. Significant autophagy induction was observed with pimozide treatment. LC3B, Beclin-1, and ATG5 up-regulation along with autolysosome formation confirmed the induction of autophagy with pimozide treatment. Inhibiting autophagy using 3-methyladenine or LC3B siRNA significantly blocked the apoptosis-inducing effects of pimozide, suggesting that pimozide mediated its apoptotic effects by inducing autophagy. Oral administration of 25 mg/kg pimozide suppressed the intracranially implanted U-87MG tumor growth by 45% in athymic nude mice. The chronic administration of pimozide showed no general signs of toxicity, and the behavioral activity of the mice remained unchanged. Taken together, these results indicate that pimozide inhibits the growth of brain cancer by autophagy-mediated apoptosis. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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Review

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20 pages, 1147 KiB  
Review
Epigenetic Perspective of Immunotherapy for Cancers
by Sunita Keshari, Praveen Barrodia and Anand Kamal Singh
Cells 2023, 12(3), 365; https://doi.org/10.3390/cells12030365 - 19 Jan 2023
Cited by 4 | Viewed by 3146
Abstract
Immunotherapy has brought new hope for cancer patients in recent times. However, despite the promising success of immunotherapy, there is still a need to address major challenges including heterogeneity in response among patients, the reoccurrence of the disease, and iRAEs (immune-related adverse effects). [...] Read more.
Immunotherapy has brought new hope for cancer patients in recent times. However, despite the promising success of immunotherapy, there is still a need to address major challenges including heterogeneity in response among patients, the reoccurrence of the disease, and iRAEs (immune-related adverse effects). The first critical step towards solving these issues is understanding the epigenomic events that play a significant role in the regulation of specific biomolecules in the context of the immune population present in the tumor immune microenvironment (TIME) during various treatments and responses. A prominent advantage of this step is that it would enable researchers to harness the reversibility of epigenetic modifications for their druggability. Therefore, we reviewed the crucial studies in which varying epigenomic events were captured with immuno-oncology set-ups. Finally, we discuss the therapeutic possibilities of their utilization for the betterment of immunotherapy in terms of diagnosis, progression, and cure for cancer patients. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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19 pages, 739 KiB  
Review
Immunotherapy: Recent Advances and Its Future as a Neoadjuvant, Adjuvant, and Primary Treatment in Colorectal Cancer
by Irene Yu, Anthony Dakwar and Kazuaki Takabe
Cells 2023, 12(2), 258; https://doi.org/10.3390/cells12020258 - 08 Jan 2023
Cited by 11 | Viewed by 3469
Abstract
Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to greatly improve patient outcomes in mismatch repair-deficient (dMMR) CRC. Now, they are part of the standard of [...] Read more.
Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to greatly improve patient outcomes in mismatch repair-deficient (dMMR) CRC. Now, they are part of the standard of care for this subset of CRC. Because of this, there has been a growing interest in the efficacy and timing of immunotherapy for other subsets of CRC, including locally advanced, metastatic, and microsatellite stable (MSS). In this review, we aim to examine the three main classes of immunotherapy for CRC—immune checkpoint inhibitors (ICIs), adoptive cell transfer therapy (ACT), and tumor vaccines—and discuss the most recent advances and future directions for each. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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20 pages, 1266 KiB  
Review
PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer
by Kunrui Zhu, Yanqi Wu, Ping He, Yu Fan, Xiaorong Zhong, Hong Zheng and Ting Luo
Cells 2022, 11(16), 2508; https://doi.org/10.3390/cells11162508 - 12 Aug 2022
Cited by 44 | Viewed by 5512
Abstract
Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are [...] Read more.
Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are continuously developed. For breast cancer patients to truly benefit from PAM pathway inhibitors, it is necessary to clarify the frequency and mechanism of abnormal alterations in the PAM pathway in different breast cancer subtypes, and further explore reliable biomarkers to identify the appropriate population for precision therapy. Some PI3K and mTOR inhibitors have been approved by regulatory authorities for the treatment of specific breast cancer patient populations, and many new-generation PI3K/mTOR inhibitors and AKT isoform inhibitors have also been shown to have good prospects for cancer therapy. This review summarizes the changes in the PAM signaling pathway in different subtypes of breast cancer, and the latest research progress about the biomarkers and clinical application of PAM-targeted inhibitors. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Therapy)
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