Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies

Sep 23, 2026

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, arise from complex oncogenic pathways and genetic abnormalities, and they often face resistance and relapse despite therapeutic advances. This review integrates precision medicine with CRISPR-based gene editing and immunotherapy, including CAR-T cells and immune checkpoint inhibitors, alongside targeted modulation of amino acid metabolism. It analyzes molecular drivers of tumor development and resistance and shows how multi-omic profiling can enable personalized treatment strategies. It also summarizes recent progress in reprogramming immune responses, editing driver mutations, and exploiting amino-acid metabolic vulnerabilities to support translational applications and improved outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages68

Reading Time2 h 51 min

AccessFree to download

Introduction

Oncogenic pathways and therapeutic challenges

Precision medicine, CRISPR and immunotherapy

Targeting amino acid metabolism

Ikhtiar et al. Discover Oncology (2025) 16:1687 [https://doi.org/10.1007/s12672-025-03535-7](https://doi.org/10.1007/s12672-025-03535-7) Discover Oncology REVIEW Open Access Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies Farhan Ikhtiar 1, Adil Jamal2* and Syed M. Safeer Mehdi Bokhari2 *Correspondence: Adil Jamal [adiljamalcemb@gmail.com](adiljamalcemb@gmail.com)[ ](adiljamalcemb@gmail.com)1University of Central Punjab, Lahore, Pakistan 2The University of Faisalabad, Faisalabad, Pakistan Abstract Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, represent a diverse group of blood cancers driven by complex oncogenic pathways and genetic aberrations. Despite advances in treatment, resistance and relapse remain significant clinical challenges. This review presents an integrative approach to blood cancer therapy, highlighting the convergence of precision medicine, CRISPRbased gene editing, immunotherapy (including CAR-T cells and immune checkpoint inhibitors), and targeted modulation of amino acid metabolism. We investigate the molecular pathways driving tumour development and resistance, highlighting how multi-omic profiling facilitates personalised therapy approaches. Recent breakthroughs in reprogramming immune responses and editing driver mutations have revolutionized therapeutic paradigms. Additionally, the metabolic dependencies of cancer cells, particularly in amino acid biosynthesis and catabolism, offer novel vulnerabilities. This meticulous synthesis outlines a framework for translational techniques that integrate molecular targeting with immunological and metabolic regulation to improve treatment effectiveness and surmount therapeutic resistance in haematologic malignancies. Keywords AML, CRISPR, Multiple myeloma, Diffuse large b-cell lymphoma, CLL 1 Introduction Blood cancers or hematologic malignancies are an extremely diverse set of cancers that affect one or more of the blood, bone marrow, or lymphatic system. Different hematopoietic cell types give birth to leukemia, lymphoma, and myeloma-related disorders, each of which has its biological characteristics, clinical signs, and therapeutic difficulties [1]. In recent decades, unprecedented advances in molecular biology, genetics, and immunotherapy have transformed diagnosis, prognosis, and treatment. Traditional chemotherapy and radiation therapy, still the cornerstones of treatment, have slowly and steadily been alternated with more modern techniques of medicine that, in combination with genomic knowledge and gene-editing technologies such as CRISPR, are targeting oncogenic drivers with extraordinary precision [2]. Leukaemia is classified as a cancer © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/. Ikhtiar et al. Discover Oncology (2025) 16:1687 Page 2 of 68 of the blood and bone marrow, characterized by an elevated prod

FAQs

Which cancer types are covered under hematologic malignancies in the review?

The review covers leukemia, lymphoma, and multiple myeloma as diverse blood cancers driven by oncogenic pathways and genetic aberrations.

How does the review connect precision medicine and gene editing to therapy?

It describes an integrative approach combining precision medicine with CRISPR-based gene editing to correct pathogenic mutations and design gene therapies with curative potential.

What role does amino acid metabolism play in the proposed therapeutic strategy?

The review highlights metabolic dependencies of cancer cells, particularly in amino acid biosynthesis and catabolism, as novel vulnerabilities for targeted modulation to improve treatment effectiveness and overcome resistance.

Sep 23, 2026

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