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Alvo em RTKs/nRTKs como estratégias terapêuticas promissoras para o tratamento do câncer de mama triplo-negativo: evidências de ensaios clínicos

  • role： First author第一作者
  • Affiliation：

    Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India

Kasshish Mehta1,  
  • Affiliation：

    Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India

Mangala Hegde1,  
  • Affiliation：

    Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India

Sosmitha Girisa1,  
  • Affiliation：

    Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India

Ravichandran Vishwa1,  
  • Affiliation：

    Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, 61421 Abha, Saudi Arabia

    BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester LE1 7RH, UK

Mohammed S. Alqahtani23,  
  • Affiliation：

    Electrical Engineering Department, College of Engineering, King Khalid University, 61421 Abha, Saudi Arabia

Mohamed Abbas4,  
  • Affiliation：

    Department of Human-Anatomy, Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Ludwig-Maximilian-University, 80336 Munich, Germany

Mehdi Shakibaei5,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore

    NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117699, Singapore

  • Email：phcgs@nus.edu.sg
  • Introduction：* Gautam Sethi phcgs@nus.edu.sg
Gautam Sethi67*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India

  • Email：kunnumakkara@iitg.ac.in
  • Introduction：Ajaikumar B. Kunnumakkara kunnumakkara@iitg.ac.in
Ajaikumar B. Kunnumakkara1*

Resumo

The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has high-lighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2(HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.

Palavras-chave

Triple-negative breast cancer (TNBC);Tyrosine kinase;clinical trial;Personalised medicine;Genetic diversity;Patient stratification

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