Molecular Underpinnings of Cancer: Pathways to Targeted Therapy

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 925

Special Issue Editors


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Guest Editor
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Interests: immuno-oncology; personalized medicine; resistance mechanisms; drug development

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Guest Editor
National Cancer Institute, Bethesda, MD, USA
Interests: tissue-based biomarkers; digital image analysis; molecular biology; gastrointestinal cancer; gynecologic cancer

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to a Special Issue of the MDPI journal ‘Life’, entitled “Molecular Underpinnings of Cancer: Pathways to Targeted Therapy”.

Cancer remains one of the leading causes of mortality worldwide, and unraveling its molecular bases is essential for improving strategies in diagnosis, prognosis, and therapy. Significant advancements have been made in finding important molecular factors that drive tumor growth; however, many areas of cancer biology are still not fully understood, especially tumor heterogeneity, immune system escape, and resistance to targeted treatments.

This Special Issue aims to advance our understanding of the molecular events governing cancer development and progression, providing a comprehensive platform of high-impact research. We welcome original articles, reviews, and perspectives covering a broad spectrum of topics, including (but not limited to) the following:

  • Oncogenes and tumor suppressors.
  • Epigenetic modifications and chromatin remodeling.
  • Roles of non-coding RNAs in cancer.
  • Tumor microenvironment interactions.
  • Dysregulated signaling pathways.
  • Cancer metabolism and metabolic reprogramming.
  • Mechanisms of DNA damage and repair.
  • Liquid biopsy biomarkers.
  • Novel molecular targets for precision oncology.

By bringing together molecular biologists, oncologists, and translational researchers, this Special Issue seeks to foster multidisciplinary dialogue and innovative findings, potentially linking fundamental discoveries with clinical applications. Our ultimate goal is to provide both a resource and inspiration for advancing molecular oncology in the era of personalized medicine.

We look forward to your valuable contribution and encourage you to submit your manuscript for consideration.

Dr. Rahul Shivahare
Dr. Joon-Yong Chung
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 250 words) can be sent to the Editorial Office for assessment.

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. Life is an international peer-reviewed open access monthly 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 2600 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

  • signaling pathways
  • tumor microenvironment
  • cancer metabolism
  • biomarkers
  • drug resistance
  • precision medicine
  • targeted therapy

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Published Papers (1 paper)

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Research

13 pages, 2741 KB  
Article
AXL-Driven Stemness and Hedgehog Signaling in HER2-Positive Breast Cancer with Acquired Trastuzumab Resistance: Synergistic Potential of AXL and HER2 Co-Targeting
by Asiye Busra Boz, Idris Er, Enric Arasanz Picher and Sneha Smarakan
Life 2026, 16(3), 371; https://doi.org/10.3390/life16030371 - 25 Feb 2026
Cited by 1 | Viewed by 619
Abstract
Stemness is a critical factor in tumor initiation, progression, metastasis, and resistance to treatment. The AXL receptor and hedgehog (Hh) signaling pathways play significant roles in regulating stemness, making them potential therapeutic targets. This study explores the involvement of AXL and hedgehog signaling [...] Read more.
Stemness is a critical factor in tumor initiation, progression, metastasis, and resistance to treatment. The AXL receptor and hedgehog (Hh) signaling pathways play significant roles in regulating stemness, making them potential therapeutic targets. This study explores the involvement of AXL and hedgehog signaling in maintaining stemness and contributing to trastuzumab resistance in HER2-positive breast cancer. The expression of AXL and Hh markers was assessed in trastuzumab-resistant SKBR3 and HCC1954 cell lines and their parental counterparts. Trastuzumab resistance was associated with upregulation of AXL expression, with the GAS6/AXL axis identified as a regulator of stemness. Although inhibition of hedgehog signaling using GANT61 did not affect AXL expression, overexpression of AXL led to increased levels of hedgehog markers (e.g., Gli1, Ptch1) and stemness markers (e.g., Sox2, Oct4, Nanog), while silencing AXL resulted in their downregulation. Furthermore, AXL overexpression enhanced stemness in resistant cells, suggesting its role in resistance mechanisms. The combination of AXL inhibition and trastuzumab treatment significantly reduced stemness and hedgehog marker expression, indicating a synergistic effect. These results emphasize the pivotal role of AXL in regulating both stemness and hedgehog signaling in HER2-positive breast cancer. The study suggests that targeting both AXL and HER2 could be a promising strategy to overcome trastuzumab resistance and improve treatment outcomes. Full article
(This article belongs to the Special Issue Molecular Underpinnings of Cancer: Pathways to Targeted Therapy)
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