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This review surveys established and emerging drug targets and resistance mechanisms, highlighting targeted options such as KRAS G12C, CLDN18.2, TROP2, and epigenetic regulators. It also outlines persistent challenges and emphasizes artificial intelligence’s growing role in cancer drug discovery and development. Overall, integrated pharmacology, clinical trials, molecular research, and AI point toward transformative oncology 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Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy  \nHarpreet Kaur1, *, Dhrubalochan Rana2, Sowvik Bag2 and Paramjeet Singh3  \n1 University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India  \n2 M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, India 3 Aurobindo Pharma, Durham, NC 27709, USA  \n*[Corresponding Author: Harpreet Kaur. Email: harpreetdoc0650@gmail.com](Corresponding Author: Harpreet Kaur. Email: harpreetdoc0650@gmail.com)[ ](Corresponding Author: Harpreet Kaur. Email: harpreetdoc0650@gmail.com)[Received: 02 August 2025](Received: 02 August 2025); [Accepted: 11 December 2025](Accepted: 11 December 2025); [Published: 19 January 2026](Published: 19 January 2026)  \nABSTRACT: The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic regulators emphasize their promise in advancing precision medicine. However, in many cases, the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions. The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology. This review seeks to elucidate recent advancements, address persisting challenges, and explore opportunities for innovative developmentsin cancer target research. Additionally, it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research. In conclusion, innovative approaches in oncology, supported by pharmacological research, ongoing clinical trials, molecular biosciences, and artificial intelligence, are poised to significantly transform cancer treatment.  \nKEYWORDS: Targeted therapy; oncological drug targets; drug resistance; epidermal growth factor receptor; artificial intelligence  \n1 Introduction  \nCancer, the most prevalent health concern in the modern era, has been among the extensively researched topics in the scientific community for many decades [1] . It is recognized as the second most significant causal factor of death, which continues to be the most serious health challenge around the world in over 60% of countries [2] . In 2020 alone, approximately 19.3 million new cases were estimated and diagnosed, and millions of people lost their lives to the disease [3] . It can be characterized by unrestrained proliferation of cells, vigorously invading their surrounding tissues and organs. Cancer can be divided into various categories depending on its histological origin, such as carcinomas, sarcomas, myeloma, lymphomas, leukemias, etc. Consequently, owing to their different cellular origins, a common therapeutic approach is ineffective in controlling their progression and management. Today, the oncological treatment options include surgery, radiation, chemotherapy, hormone therapy, targeted therapy, and immunotherapy, all of which are used either individually or in multimodality [4] . Several scientific and technological fields, like  \nCopyright © 2026 The Authors. Published by Tech Science Press.  \nThis work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work i","cbCaiaulpWLsa3ms","https://ap.wps.com/l/cbCaiaulpWLsa3ms","pdf",10430146,48,"English","# ABSTRACT\n# KEYWORDS\n# Introduction","[{\"question\":\"What does the review focus on regarding cancer therapy?\",\"answer\":\"It provides a comprehensive, up-to-date examination of both established and emerging oncological drug targets and the mechanisms behind treatment resistance.\"},{\"question\":\"Which targeted therapies are highlighted as promising for precision medicine?\",\"answer\":\"The review emphasizes KRAS G12C, CLDN18.2, TROP2, and epigenetic regulators as novel targeted options that may advance precision oncology.\"},{\"question\":\"How does resistance affect the effectiveness of targeted interventions?\",\"answer\":\"In many cases, resistance mechanisms associated with these interventions reduce or undermine their ability to carry out their intended functions.\"}]","A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy | PDF",1790060903,121]