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Fifty Years of Targeted Therapy in Cancer: Past, Present and...
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Fifty Years of Targeted Therapy in Cancer: Past, Present and Future

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

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 12102

Special Issue Editor

Dr. Pritam Sadhukhan

E-Mail Website
Guest Editor
Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Interests: cancer signaling; cancer immunology; cancer metabolism; targeted therapy; repurposed drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. There are many different types of cancer, including lung cancer, breast cancer, prostate cancer, and skin cancer. Each type of cancer is caused by a specific set of genetic mutations and can have different risk factors, symptoms, and treatment options.

Treatment options for cancer include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, and supportive care. The choice of treatment will depend on the type and stage of the cancer, as well as the patient's overall health. However, the road is not straight, and there are multiple obstacles owing to the heterogeneity and plasticity of the cells in the tumor microenvironment. Researchers, in collaboration with physicians and surgeons, are toiling hard to combat therapeutic resistance. During the last few decades, developments have been made to understand the signaling mechanism behind therapeutic resistance, and researchers have found improved therapeutic efficacy when specific molecular pathways are targeted in the cancer cells and immune cells in the tumor microenvironment (TME).

Targeted therapy is a type of cancer treatment that targets specific molecules or proteins within cancer cells that are involved in the growth and spread of the tumor. These therapies are designed to inhibit the growth and spread of cancer cells while minimizing harm to normal cells. Examples of targeted therapies include monoclonal antibodies, small molecule inhibitors, and kinase inhibitors. These therapies are often used in combination with other treatments such as chemotherapy, radiation therapy, and surgery.

This Research Topic will provide an academic platform to discuss how different candidate therapeutic drugs can be used against deregulated regulatory pathways in TME. We invite authors to contribute original research and review articles testing the mechanism of action of natural and chemically synthesized bioactive products on various cancer types through the regulation of different molecular pathways (including suppression and overcoming resistance).

We aim to particularly focus on the recent advances in the development of different candidate molecules on different cancer types and invite the submission of comprehensive research articles, review articles, mini reviews and commentaries on the following potential topics:

(1) Significance of different regulatory pathways in cancer initiation, cancer progression, the development of chemotherapeutic resistance and immune evasion.

(2) Characteristic nature of the different regulatory pathways and significance of these pathways with respect to cancer types (as well as subtypes), stages and other exogenous or endogenous factors.

(3) Novel signaling molecules regulating the maintenance and proliferation of cancer cells and immune evasion.

(4) Novel drug candidates affecting tumor immune microenvironment.

(5) Advancements in and updates to the current drug candidates correlated with cancer stem cells’ regulatory properties and immune evasion

(6) Systemic reviews or meta-analysis of the approved drug candidates in clinical research stage with growth regulatory properties and affecting the responsiveness of immune therapy.

Since IJMS is a journal of molecular science, pure clinical studies are thus not suitable for our journal. However, clinical submissions with biomolecular experiments are welcomed.

Dr. Pritam Sadhukhan
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

  • tumor microenvironment
  • immune suppression
  • targeted therapy
  • immune checkpoint blockers
  • epigenetic regulators
  • macrophage polarization
  • cancer stem cells
  • therapeutic resistance
  • tumor immune microenvironment
  • immunotherapy
  • repurposed drugs
  • oxidative stress

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Published Papers (5 papers)

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Review

23 pages, 1595 KiB  
Review
Cracking the Codes behind Cancer Cells’ Immune Evasion
by Nikita Mundhara and Pritam Sadhukhan
Int. J. Mol. Sci. 2024, 25(16), 8899; https://doi.org/10.3390/ijms25168899 - 15 Aug 2024
Viewed by 1675
Abstract
Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps in tumor progression. The tumor microenvironment (TME) is in constant flux due to the tumor’s ability to release signals that affect it, while immune cells within it can [...] Read more.
Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps in tumor progression. The tumor microenvironment (TME) is in constant flux due to the tumor’s ability to release signals that affect it, while immune cells within it can impact cancer cell behavior. Cancer cells undergo several changes, which can change the enrichment of different immune cells and modulate the activity of existing immune cells in the tumor microenvironment. Cancer cells can evade immune surveillance by downregulating antigen presentation or expressing immune checkpoint molecules. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better outcomes, and robust immune responses can control tumor growth. On the contrary, increased enrichment of Tregs, myeloid-derived suppressor cells, and M2-like anti-inflammatory macrophages can hinder effective immune surveillance and predict poor prognosis. Overall, understanding these immune evasion mechanisms guides therapeutic strategies. Researchers aim to modulate the TME to enhance immune surveillance and improve patient outcomes. In this review article, we strive to summarize the composition of the tumor immune microenvironment, factors affecting the tumor immune microenvironment (TIME), and different therapeutic modalities targeting the immune cells. This review is a first-hand reference to understand the basics of immune surveillance and immune evasion. Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
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20 pages, 1313 KiB  
Review
Applications of Modified Mesenchymal Stem Cells as Targeted Systems against Tumor Cells
by Elsa N. Garza Treviño, Adriana G. Quiroz Reyes, Paulina Delgado Gonzalez, Juan Antonio Rojas Murillo, Jose Francisco Islas, Santiago Saavedra Alonso and Carlos A. Gonzalez Villarreal
Int. J. Mol. Sci. 2024, 25(14), 7791; https://doi.org/10.3390/ijms25147791 - 16 Jul 2024
Viewed by 1265
Abstract
Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects [...] Read more.
Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects on the tissue microenvironment. MSCs have been widely investigated to exploit their antitumor target delivery system. They can be genetically modified to overexpress genes and selectively or more efficiently eliminate tumor cells. Current approaches tend to produce more effective and safer therapies using MSCs or derivatives; however, the effect achieved by engineered MSCs in solid tumors is still limited and depends on several factors such as the cell source, transgene, and tumor target. This review describes the progress of gene and cell therapy focused on MSCs as a cornerstone against solid tumors, addressing the different MSC-engineering methods that have been approached over decades of research. Furthermore, we summarize the main objectives of engineered MSCs against the most common cancers and discuss the challenges, limitations, risks, and advantages of targeted treatments combined with conventional ones. Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
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28 pages, 5328 KiB  
Review
Plasma Metabolite Profiling in the Search for Early-Stage Biomarkers for Lung Cancer: Some Important Breakthroughs
by Jill Meynen, Peter Adriaensens, Maarten Criel, Evelyne Louis, Karolien Vanhove, Michiel Thomeer, Liesbet Mesotten and Elien Derveaux
Int. J. Mol. Sci. 2024, 25(9), 4690; https://doi.org/10.3390/ijms25094690 - 25 Apr 2024
Viewed by 1415
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking [...] Read more.
Lung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster, and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already been shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterized by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation to their metabolic pathways and in light of the altered cancer metabolism. Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
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36 pages, 516 KiB  
Review
Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future
by Hanley N. Abramson
Int. J. Mol. Sci. 2023, 24(21), 15674; https://doi.org/10.3390/ijms242115674 - 27 Oct 2023
Cited by 6 | Viewed by 4611
Abstract
The landscape of therapeutic measures to treat multiple myeloma has undergone a seismic shift since the dawn of the current century. This has been driven largely by the introduction of new classes of small molecules, such as proteasome blockers (e.g., bortezomib) and immunomodulators [...] Read more.
The landscape of therapeutic measures to treat multiple myeloma has undergone a seismic shift since the dawn of the current century. This has been driven largely by the introduction of new classes of small molecules, such as proteasome blockers (e.g., bortezomib) and immunomodulators (e.g., lenalidomide), as well as by immunotherapeutic agents starting with the anti-CD38 monoclonal antibody daratumumab in 2015. Recently, other immunotherapies have been added to the armamentarium of drugs available to fight this malignancy. These include the bispecifics teclistamab, talquetamab, and elranatamab, and the chimeric antigen receptor (CAR) T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). While the accumulated benefits of these newer agents have resulted in a more than doubling of the disease’s five-year survival rate to nearly 60% and improved quality of life, the disease remains incurable, as patients become refractory to the drugs and experience relapse. This review covers the current scope of antimyeloma immunotherapeutic agents, both those in clinical use and in development. Included in the discussion are additional monoclonal antibodies (mAbs), antibody–drug conjugates (ADCs), bi- and multitargeted mAbs, and CAR T-cells and emerging natural killer (NK) cells, including products intended for “off-the-shelf” (allogeneic) applications. Emphasis is placed on the benefits of each along with the challenges that need to be surmounted if MM is to be cured. Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
13 pages, 1577 KiB  
Review
Targeting Inhibitor of Apoptosis Proteins to Overcome Chemotherapy Resistance—A Marriage between Targeted Therapy and Cytotoxic Chemotherapy
by Tiago Barroso, Cecília Melo-Alvim, Leonor Abreu Ribeiro, Sandra Casimiro and Luís Costa
Int. J. Mol. Sci. 2023, 24(17), 13385; https://doi.org/10.3390/ijms241713385 - 29 Aug 2023
Cited by 5 | Viewed by 1893
Abstract
Precision oncology is the ultimate goal of cancer treatment, i.e., to treat cancer and only cancer, leaving all the remaining cells and tissues as intact as possible. Classical chemotherapy and radiotherapy, however, are still effective in many patients with cancer by effectively inducing [...] Read more.
Precision oncology is the ultimate goal of cancer treatment, i.e., to treat cancer and only cancer, leaving all the remaining cells and tissues as intact as possible. Classical chemotherapy and radiotherapy, however, are still effective in many patients with cancer by effectively inducing apoptosis of cancer cells. Cancer cells might resist apoptosis via the anti-apoptotic effects of the inhibitor of apoptosis proteins. Recently, the inhibitors of those proteins have been developed with the goal of enhancing the cytotoxic effects of chemotherapy and radiotherapy, and one of them, xevinapant, has already demonstrated effectiveness in a phase II clinical trial. This class of drugs represents an example of synergism between classical cytotoxic chemo- and radiotherapy and new targeted therapy. Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
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