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New Insights into Anti-cancer Drug Discovery and Development
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New Insights into Anti-cancer Drug Discovery and Development

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 4677

Special Issue Editor

Dr. Ki-cheong Park

E-Mail Website
Guest Editor
College of Medicine, Yonsei University, Seoul, Republic of Korea
Interests: anti-cancer drug resistance; cancer recurrence; cancer metastasis; cancer stem cells; target valida-tion; target identification

Special Issue Information

Dear Colleagues, 

Cancer drug discovery has greatly advanced since its earliest steps. However, rare occurrences of anti-cancer drug-resistant cancer show a poor prognosis via recurrence or metastasis, and these consequences can be associated with patient death. Various studies have shown that recurrent or metastatic cancer is refractory to most medical treatments. These refractory cancers are usually slow; however, following anaplasia of the injury, they are altered into poorly differentiated and undifferentiated cancer, described by a sharp expansion involving a poor prognosis. The stemness and aggressiveness of refractory cancer has not yet been revealed. Studies looking at the outcomes from the advancement of anti-cancer drugs have described that pre-operative chemotherapy can extend survival rates after surgery. Nonetheless, no selective therapeutic options have been accepted as the basal adjuvant or neoadjuvant background for drug-resistant cancer, and a substantial number of anti-cancer drug-resistant cancer patients have died; therefore, unmet medical needs have consistently increased. Refractory cancer due to drug resistance, which mediates metastasis and recurrence, is a decisive part of unmet medical needs. Anti-cancer drug resistance remains a fundamental challenge in the treatment of patients with refractory cancer. For these reasons, anti-cancer drug resistance in refractory cancer represents a primary challenge in cancer therapy. Submission to this Special Issue could be potentially exploited as a breakthrough clinical solution to drug-resistant cancer.

Dr. Ki-cheong Park
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • anti-cancer drug resistant
  • cancer recurrence
  • cancer metastasis
  • cancer stem cells
  • target validation
  • target identification
  • metabolic reprogramming of cancer stem cells
  • unmet medical needs

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Published Papers (3 papers)

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Research

16 pages, 2820 KiB  
Article
New Small-Molecule SERCA Inhibitors Enhance Treatment Efficacy in Lenvatinib-Resistant Papillary Thyroid Cancer
by Jungmin Kim, Hang-Seok Chang, Hyeok Jun Yun, Ho-Jin Chang and Ki Cheong Park
Int. J. Mol. Sci. 2024, 25(19), 10646; https://doi.org/10.3390/ijms251910646 - 3 Oct 2024
Viewed by 699
Abstract
Papillary thyroid cancer (PTC) is one of the most treatable forms of cancer, with many cases being fully curable. However, resistance to anticancer drugs often leads to metastasis or recurrence, contributing to the failure of cancer therapy and, ultimately, patient mortality. The mechanisms [...] Read more.
Papillary thyroid cancer (PTC) is one of the most treatable forms of cancer, with many cases being fully curable. However, resistance to anticancer drugs often leads to metastasis or recurrence, contributing to the failure of cancer therapy and, ultimately, patient mortality. The mechanisms underlying molecular differences in patients with metastatic or recurrent PTC, particularly those resistant to anticancer drugs through epigenetic reprogramming, remain poorly understood. Consequently, refractory PTC presents a critical challenge, and effective therapeutic strategies are urgently needed. Therefore, this study aimed to identify small-molecule inhibitors to enhance treatment efficacy in lenvatinib-resistant PTC. We observed an increase in sarco/endoplasmic reticulum calcium ATPase (SERCA) levels in patient-derived lenvatinib-resistant PTC cells compared with lenvatinib-sensitive ones, highlighting its potential as a therapeutic target. We subsequently identified two SERCA inhibitors [candidates 40 (isoflurane) and 42 (ethacrynic acid)] through in silico screening. These candidates demonstrated significant tumor shrinkage in a xenograft tumor model and reduced cell viability in patient-derived lenvatinib-resistant PTC cells when used in combination with lenvatinib. Our findings have potential clinical value for the development of new combination therapies to effectively target highly malignant, anticancer drug-resistant cancers. Full article
(This article belongs to the Special Issue New Insights into Anti-cancer Drug Discovery and Development)
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15 pages, 4010 KiB  
Article
Modeling the Binding of Anticancer Peptides and Mcl-1
by Shamsa Husain Ahmed Alhammadi, Bincy Baby, Priya Antony, Amie Jobe, Raghad Salman Mohammed Humaid, Fatema Jumaa Ahmed Alhammadi and Ranjit Vijayan
Int. J. Mol. Sci. 2024, 25(12), 6529; https://doi.org/10.3390/ijms25126529 - 13 Jun 2024
Viewed by 961
Abstract
Mcl-1 (myeloid cell leukemia 1), a member of the Bcl-2 family, is upregulated in various types of cancer. Peptides representing the BH3 (Bcl-2 homology 3) region of pro-apoptotic proteins have been demonstrated to bind the hydrophobic groove of anti-apoptotic Mcl-1, and this interaction [...] Read more.
Mcl-1 (myeloid cell leukemia 1), a member of the Bcl-2 family, is upregulated in various types of cancer. Peptides representing the BH3 (Bcl-2 homology 3) region of pro-apoptotic proteins have been demonstrated to bind the hydrophobic groove of anti-apoptotic Mcl-1, and this interaction is responsible for regulating apoptosis. Structural studies have shown that, while there is high overall structural conservation among the anti-apoptotic Bcl-2 (B-cell lymphoma 2) proteins, differences in the surface groove of these proteins facilitates binding specificity. This binding specificity is crucial for the mechanism of action of the Bcl-2 family in regulating apoptosis. Bim-based peptides bind specifically to the hydrophobic groove of Mcl-1, emphasizing the importance of these interactions in the regulation of cell death. Molecular docking was performed with BH3-like peptides derived from Bim to identify high affinity peptides that bind to Mcl-1 and to understand the molecular mechanism of their interactions. The interactions of three identified peptides, E2gY, E2gI, and XXA1_F3dI, were further evaluated using 250 ns molecular dynamics simulations. Conserved hydrophobic residues of the peptides play an important role in their binding and the structural stability of the complexes. Understanding the molecular basis of interaction of these peptides will assist in the development of more effective Mcl-1 specific inhibitors. Full article
(This article belongs to the Special Issue New Insights into Anti-cancer Drug Discovery and Development)
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17 pages, 2717 KiB  
Article
Enhanced Production of Nitrogenated Metabolites with Anticancer Potential in Aristolochia manshuriensis Hairy Root Cultures
by Yury N. Shkryl, Galina K. Tchernoded, Yulia A. Yugay, Valeria P. Grigorchuk, Maria R. Sorokina, Tatiana Y. Gorpenchenko, Olesya D. Kudinova, Anton I. Degtyarenko, Maria S. Onishchenko, Nikita A. Shved, Vadim V. Kumeiko and Victor P. Bulgakov
Int. J. Mol. Sci. 2023, 24(14), 11240; https://doi.org/10.3390/ijms241411240 - 8 Jul 2023
Cited by 4 | Viewed by 2456
Abstract
Aristolochia manshuriensis is a relic liana, which is widely used in traditional Chinese herbal medicine and is endemic to the Manchurian floristic region. Since this plant is rare and slow-growing, alternative sources of its valuable compounds could be explored. Herein, we established hairy [...] Read more.
Aristolochia manshuriensis is a relic liana, which is widely used in traditional Chinese herbal medicine and is endemic to the Manchurian floristic region. Since this plant is rare and slow-growing, alternative sources of its valuable compounds could be explored. Herein, we established hairy root cultures of A. manshuriensis transformed with Agrobacterium rhizogenes root oncogenic loci (rol)B and rolC genes. The accumulation of nitrogenous secondary metabolites significantly improved in transgenic cell cultures. Specifically, the production of magnoflorine reached up to 5.72 mg/g of dry weight, which is 5.8 times higher than the control calli and 1.7 times higher than in wild-growing liana. Simultaneously, the amounts of aristolochic acids I and II, responsible for the toxicity of Aristolochia species, decreased by more than 10 fold. Consequently, the hairy root extracts demonstrated pronounced cytotoxicity against human glioblastoma cells (U-87 MG), cervical cancer cells (HeLa CCL-2), and colon carcinoma (RKO) cells. However, they did not exhibit significant activity against triple-negative breast cancer cells (MDA-MB-231). Our findings suggest that hairy root cultures of A. manshuriensis could be considered for the rational production of valuable A. manshuriensis compounds by the modification of secondary metabolism. Full article
(This article belongs to the Special Issue New Insights into Anti-cancer Drug Discovery and Development)
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