Advancements and Challenges in Anticancer Targeted Therapy with Small Molecules

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 667

Special Issue Editor


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Guest Editor
Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Medyczna 9, 30-688 Kraków, Poland
Interests: anticancer activity; small molecules; plant phenolics; leukemia; apoptosis; cell cycle; DNA damage; flow cytometry

Special Issue Information

Dear Colleagues,

Small molecules are chemical compounds with masses < 900 Da. Due to their small size, they easily penetrate the cell membrane and interact not only with membrane receptors but also with intracellular targets. They are easily distributed in the body and metabolized to an active drug. Small molecules constitute the majority of manufactured drugs and are mainly taken by patients orally.

Small molecules are successfully used as molecularly targeted drugs in the treatment of some cancers, as is the case with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors.

Small molecules have been developed for many therapeutic cancer targets. Examples include receptor tyrosine kinase inhibitors and non-receptor tyrosine kinase inhibitors, serine/threonine kinase inhibitors, proteasome inhibitors, inhibitors for epigenetic regulatory proteins, BCL-2 inhibitors, and matrix metalloproteinase inhibitors.

The great success achieved in the treatment of CML cannot be achieved in many other cancer diseases, possibly due to the heterogeneous expression of the therapeutic targets of cancer cells in patients. Another problem is resistance to therapy using small molecules, both existing ones and those acquired during treatment.

To solve these problems, we need to identify new predictive biomarkers, develop small molecules targeted at resistance mutations and cancer stem cells or use multitarget drugs.

This Special Issue will present research on new small molecules as molecular targeted therapies in cancer treatment, as well as research on new ways to bypass the problems of acquired resistance to small molecules. Research on new therapeutic targets is also welcome.

Dr. Monika Papiez
Guest Editor

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Keywords

  • small molecules
  • cancer
  • anticancer targeted therapy
  • cancer resistance
  • cancer growth blockers

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Published Papers (1 paper)

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Review

18 pages, 841 KB  
Review
Cutaneous Adverse Events of Tyrosine Kinase Inhibitors in Endocrine Tumors: Clinical Features, Mechanisms, and Management Strategies
by Marta Marino, Francois Rosset, Alice Nervo, Alessandro Piovesan, Valentina Pala, Elisa Vaccaro, Luca Mastorino, Aldo E. Calogero and Emanuela Arvat
Biomedicines 2025, 13(12), 3044; https://doi.org/10.3390/biomedicines13123044 - 11 Dec 2025
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Abstract
Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs [...] Read more.
Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs used in endocrine oncology and provide practical, multidisciplinary guidance for prevention and management. Methods: Narrative synthesis of clinical trial reports, post-marketing studies, and specialty guidelines pertinent to lenvatinib, vandetanib, cabozantinib, and other commonly used TKIs, integrating dermatologic and endocrine perspectives on mechanisms and care pathways. Results: VEGFR-targeted TKIs frequently cause hand–foot skin reaction, xerosis, fissuring, paronychia, and impaired wound healing; multikinase inhibition also produces alopecia, pigmentary changes, and mucositis. Epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) inhibition with vandetanib is associated with acneiform eruption, photosensitivity, and nail fragility. Pathogenesis reflects on-target inhibition of VEGF/EGFR signaling leading to keratinocyte dysfunction, vascular fragility, and altered eccrine mechanics. Early risk stratification, patient education, and bundle-based prophylaxis (emollients, keratolytics, urea-based creams, sun protection) reduce incidence and severity. Grade-based algorithms combining topical corticosteroids/antibiotics, dose interruptions or reductions, and short systemic courses (e.g., doxycycline, antihistamines) enable symptom control while maintaining anticancer intensity. Close coordination around procedures minimizes wound-healing complications. Conclusions: Dermatologic toxicities are predictable, mechanism-linked, and manageable with proactive, multidisciplinary care. Standardized prevention and treatment pathways tailored to specific TKIs—particularly lenvatinib, vandetanib, and cabozantinib—can preserve dose intensity, optimize quality of life, and sustain antineoplastic efficacy. Full article
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