Overcoming Drug Resistance in Solid Tumors: Novel Targets and Combination Strategies

Adaptive drug resistance represents one of the most critical barriers to durable responses in cancer therapy. Unlike static genetic resistance, adaptive resistance involves dynamic, often reversible, mechanisms by which tumor cells evade treatment through phenotypic remodeling, signaling pathway rewiring, and microenvironmental interactions.This Research Topic aims to compile cutting-edge research that illuminates these adaptive processes and translates mechanistic insights into actionable pharmacological strategies. By focusing on novel therapeutic targets and rational combination approaches, this collection will provide a platform for advancing the next generation of cancer treatments.We welcome submissions of Original Research, Reviews, Perspectives, and Clinical Trials that explore adaptive resistance across a spectrum of solid tumors, including but not limited to prostate, lung, breast, bladder, kidney, colorectal, and pancreatic cancers. Contributions may address resistance to targeted therapies, chemotherapy, immunotherapy, or hormone therapy, with an emphasis on understanding the underlying molecular and cellular adaptations. We are particularly interested in manuscripts covering the following key themes:• Mechanisms of Adaptive Resistance: Dynamic signaling and epigenetic adaptations under therapeutic pressure; the role of the tumor microenvironment and immune evasion in fostering resistance; and non-genetic plasticity, including drug-tolerant persister states and phenotypic switching.• Novel Target Discovery and Validation: Identification of key drivers and dependencies in adaptive resistance pathways; functional validation of emerging targets using preclinical models; and biomarker development for predicting and monitoring adaptive resistance.• Innovative Combination Strategies: Rational design of drug combinations to prevent or reverse resistance; immunotherapy-based combinations and microenvironment modulation; and metabolic targeting and chronotherapy approaches.• Translational and Predictive Tools: Advanced preclinical models (e.g., organoids, PDX, spatial omics); computational and AI-driven approaches to model resistance trajectories; and pharmacokinetic/pharmacodynamic (PK/PD) modeling for combination therapy optimization.Please note:• Frontiers’ journals require that manuscripts primarily comprising computational studies of public data, such as NHANES or Mendelian Randomization studies, must include appropriate validation. Please refer to the Frontiers Standards for research methodology policy), for more information. Manuscripts not adhering to these standards will not be considered.• The Pharmacology of Anti-Cancer Drugs section does not consider manuscripts focused on anti-cancer natural product research or traditional medicine-derived pharmacological approaches, as these topics may not align with the section's focus on the development and improvement of cancer drug treatments. Additionally, submissions centered on cancer prognosis or side effects of cancer therapies are excluded, as they do not directly pertain to the pharmacological aspects of anti-cancer drugs. Authors should ensure that their submissions provide evidence of significant selectivity towards cancer cells, demonstrate applicability on multiple cancer cell lines, and describe the composition and stability of study materials in detail. Topic editors: Bo Chen, Hongye Zou, Xiqi Peng Source: https://www.frontiersin.org/research-topics/79415/overcoming-drug-resistance-in-solid-tumors-novel-targets-and-combination-strategies