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Special Issue "Cancer Chemotherapy: Combination with Inhibitors"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 6114

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Special Issue Editors

Dr. Mara Cirone

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Guest Editor

Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Interests: herpesviruses; viral oncology; autophagy and unfolded protein response
Special Issues, Collections and Topics in MDPI journals

Dr. Gabriella D'Orazi

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Guest Editor

1. Department of Neuroscience and Imaging, University G. D’Annunzio, 66013 Chieti, Italy
2. Unit of Cellular Network and Therapeutic Innovation, Department of Research, Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: tumor biology; molecular oncology; oncosuppressor p53; autophagy; hypoxia; oxidative stress; tumor microenvironment; glioblastoma; personalized medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite you to contribute to this Special Issue of Cancers entitled “Cancer Chemotherapy: Combination with Inhibitors”.

Cancer is among the leading causes of mortality worldwide. Despite advances in cancer treatments, the development of drug resistance often occurs enabling cancer cells to avoid senescence or apoptosis and inducing disease recurrence and progression. Several different molecular pathways have been implicated in the development of resistance, including those regulating stress responses, such as autophagy, unfolded protein response (UPR), DNA damage response (DDR), antioxidant response, and heat shock response (HSR). Unfortunately, following the inhibition of one of the oncogenic pathways, cancer cells may hyperactivate others to keep surviving. Therefore, to combat drug resistance, combination therapies targeting several molecular pathways and their-induced protective processes seem to be more promising than a single targeted therapy especially if they result also in anti-cancer immune activation.

This Special Issue aims to collect research articles, Reviews and Communications focused on (but not limited to) experimental studies in the research area of chemoresistance and combination therapies with inhibitors to overcome or prevent potential drug resistance.

We look forward to receiving your contributions.

Dr. Mara Cirone
Dr. Gabriella D’Orazi
Guest Editors

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. Cancers 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 2900 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.

Published Papers (5 papers)

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Research

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Open AccessArticle

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

Oana Gabriela Trifănescu

Dan Mitrea

Laurenția Nicoleta Galeș

Ana Ciornei

Mihai-Andrei Păun

Ioana Butnariu

Raluca Alexandra Trifănescu

and

Rodica Maricela Anghel

Cancers 2023, 15(9), 2508; https://doi.org/10.3390/cancers15092508 - 27 Apr 2023

Viewed by 933

Abstract

Leptomeningeal metastases (LM) are a rare but rapidly fatal complication defined by the spread of tumor cells within the leptomeninges and the subarachnoid space, found in approximately 10% of patients with HER2-positive breast cancers. This pilot study evaluated the efficacy of local treatment with intrathecal Trastuzumab (IT) added to systemic treatment. The oncologic outcome of 14 patients with HER2-positive LM is reported. Seven received IT, and seven received standard of care (SOC). The mean number of IT cycles administered was 12.14 ± 4.00. The response rate to CNS after IT treatment + SOC was 71.4%, and three patients (42.8%) obtained durable responses lasting more than 12 months. The median progression-free survival (mPFS) after LM diagnosis was six months, and the median overall survival (mOS) was ten months. The mean values of the PFS in favor of IT therapy (10.6 mo vs. 6.6 mo) and OS (13.7 vs. 9.3 mo) suggest a non-negligible investigation direction in the sense of exploiting intrathecal administration as a possible treatment modality in these patients. Adverse events reported were local pain related to intrathecal administration and one case of arachnoiditis, hematoma, and CSF fistulae. Intrathecal administration of Trastuzumab, alongside systemic treatment and radiotherapy, might improve oncologic outcomes in LM HER2-positive breast cancer with manageable toxicity. Full article

(This article belongs to the Special Issue Cancer Chemotherapy: Combination with Inhibitors)

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Open AccessArticle

Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited

Ourania N. Kostopoulou

Stefan Holzhauser

and

Tina Dalianis

Cancers 2023, 15(1), 93; https://doi.org/10.3390/cancers15010093 - 23 Dec 2022

Cited by 3 | Viewed by 1374

Abstract

Human papillomavirus positive (HPV⁺) tonsillar and base of tongue cancer (TSCC/BOTSCC) is rising in incidence, but chemoradiotherapy is not curative for all. Therefore, targeted therapy with PI3K (BYL719), PARP (BMN-673), and WEE1 (MK-1775) inhibitors alone or combined was pursued with or without 10 Gy and their effects were analyzed by viability, proliferation, and cytotoxicity assays on the TSCC/BOTSCC cell lines HPV⁺ UPCI-SCC-154 and HPV⁻ UT-SCC-60A. Effective single drug/10 Gy combinations were validated on additional TSCC lines. Finally, APR-246 was assessed on several TSCC/BOTSCC cell lines. BYL719, BMN-673, and MK-1775 treatments induced dose dependent responses in HPV⁺ UPCI-SCC-154 and HPV⁻ UT-SCC-60A and when combined with 10 Gy, synergistic effects were disclosed, as was also the case upon validation. Using BYL719/BMN-673, BYL719/MK-1775, or BMN-673/MK-1775 combinations on HPV⁺ UPCI-SCC-154 and HPV⁻ UT-SCC-60A also induced synergy compared to single drug administrations, but adding 10 Gy to these synergistic drug combinations had no further major effects. Low APR-246 concentrations had limited usefulness. To conclude, synergistic effects were disclosed when complementing single BYL719 BMN-673 and MK-1775 administrations with 10 Gy or when combining the inhibitors, while adding 10 Gy to the latter did not further enhance their already additive/synergistic effects. APR-246 was suboptimal in the present context. Full article

(This article belongs to the Special Issue Cancer Chemotherapy: Combination with Inhibitors)

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Review

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Open AccessReview

Crosstalk between Microtubule Stabilizing Agents and Prostate Cancer

Qiao-Hong Chen

Cancers 2023, 15(13), 3308; https://doi.org/10.3390/cancers15133308 - 23 Jun 2023

Viewed by 547

Abstract

A variety of microtubule-stabilizing cytotoxic agents (MSA) with diverse chemical scaffolds have been discovered from marine sponges, microorganisms, and plants. Two MSAs, docetaxel and cabazitaxel, are the exclusive chemotherapeutics that convey a survival benefit in patients with castration-resistant prostate cancer (CRPC). Additional MSAs have been investigated for their potential in treating prostate cancer in both clinical and preclinical settings. Independent of promoting mitotic arrest, MSAs can suppress the nuclear accumulation of androgen receptor (AR), which is the driving force for prostate cancer cell growth and progression. The alternative mechanism not only helps to better understand the clinical efficacy of docetaxel and cabazitaxel for AR-driven CRPC but also provides an avenue to seek better treatments for various forms of prostate cancer. The dual mechanisms of action enable MSAs to suppress AR-null prostate cancer cell proliferation by cell mitosis pathway and to interfere with the AR signaling pathway in AR positive cells. MSA chemotherapeutics, being administered alone or in combination with other therapeutics, may serve as the optimal therapeutic option for patients with either castration-sensitive or castration-resistant prostate cancer. This review provides an overview of the anti-prostate cancer profiles (including preclinical and clinical studies, and clinical use) of diverse MSAs, as well as the mechanism of action. Full article

(This article belongs to the Special Issue Cancer Chemotherapy: Combination with Inhibitors)

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Open AccessReview

HIPK2 as a Novel Regulator of Fibrosis

Alessia Garufi

Giuseppa Pistritto

and

Gabriella D’Orazi

Cancers 2023, 15(4), 1059; https://doi.org/10.3390/cancers15041059 - 07 Feb 2023

Cited by 2 | Viewed by 1382

Abstract

Fibrosis is an unmet medical problem due to a lack of evident biomarkers to help develop efficient targeted therapies. Fibrosis can affect almost every organ and eventually induce organ failure. Homeodomain-interacting protein kinase 2 (HIPK2) is a protein kinase that controls several molecular pathways involved in cell death and development and it has been extensively studied, mainly in the cancer biology field. Recently, a role for HIPK2 has been highlighted in tissue fibrosis. Thus, HIPK2 regulates several pro-fibrotic pathways such as Wnt/β-catenin, TGF-β and Notch involved in renal, pulmonary, liver and cardiac fibrosis. These findings suggest a wider role for HIPK2 in tissue physiopathology and highlight HIPK2 as a promising target for therapeutic purposes in fibrosis. Here, we will summarize the recent studies showing the involvement of HIPK2 as a novel regulator of fibrosis. Full article

(This article belongs to the Special Issue Cancer Chemotherapy: Combination with Inhibitors)

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Open AccessReview

PARP Inhibitors and Proteins Interacting with SLX4

Lars Petter Jordheim

Cancers 2023, 15(3), 997; https://doi.org/10.3390/cancers15030997 - 03 Feb 2023

Viewed by 1437

Abstract

PARP inhibitors are small molecules currently used with success in the treatment of certain cancer patients. Their action was first shown to be specific to cells with DNA repair deficiencies, such as BRCA-mutant cancers. However, recent work has suggested clinical interest of these drugs beyond this group of patients. Preclinical data on relationships between the activity of PARP inhibitors and other proteins involved in DNA repair exist, and this review will only highlight findings on the SLX4 protein and its interacting protein partners. As suggested from these available data and depending on further validations, new treatment strategies could be developed in order to broaden the use for PARP inhibitors in cancer patients. Full article

(This article belongs to the Special Issue Cancer Chemotherapy: Combination with Inhibitors)

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