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Drug susceptibility testing of circulating lung cancer cells for personalized treatment

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Abstract

The presence of Circulating tumor cells (CTCs) has been proven to be correlated with disease progression and the patient’s response to treatment. However, the culture of CTCs for clinical utility is still a big challenge. We have developed a short-term method that enables CTCs culture and provides an opportunity to monitor drug susceptibility testing in individual patients. In a proof-of-concept study, we established a unique method using Matrigel® coated in 96 well plate to enable cancer cell clusters to attach and proliferate. The culture method using Matrigel® provides in vitro conditions and improves the attachment and differentiation of anchorage-dependent epithelial cells proliferation and mimics the tumor microenvironment. We further treated the cells attached to Matrigel® with the same drug regimen as the patient has undergone. Around 30.7% of the CTCs were viable after the drug treatment. We also correlated the decrease in cell viability after drug treatment with the reduction in the pleural effusion of the patient as seen by the images obtained from CT scans pre-and post-treatment. Moreover, as per the RECIST criterion, the patient had exhibited a positive response to the treatment. The short-term culturing of CTC along with the drug susceptibility testing offers a novel method to predict patient response to the treatment and could be utilized for screening suitable drug combinations for personalized treatment.

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Acknowledgements

PK is a recipient of the Ramanujan Fellowship awarded by the Department of Science and Technology (DST), Government of India. AB is the recipient of SRF from the Council of Scientific & Industrial Research (CSIR), Government of India. The authors declare no potential conflicts of interest.

Funding

This study is not funded by any funding agencies.

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Authors and Affiliations

  1. Institute of Bioinformatics, International Technology Park, Bengaluru, Karnataka, 560066, India

    Ajay Balakrishnan & Prashant Kumar

  2. Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India

    Ajay Balakrishnan & Prashant Kumar

  3. Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, 560029, India

    Antony George Francis Thottian & K. Govind Babu

  4. Consultant Medical Oncologist, HCG Cancer Hospital, Bangalore, 560027, India

    K. Govind Babu

  5. Karkinos Healthcare Pvt Ltd., Vidyavihar (W), Mumbai, Maharashtra, 400086, India

    Prashant Kumar

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  1. Ajay Balakrishnan
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  2. Antony George Francis Thottian
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  3. K. Govind Babu
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  4. Prashant Kumar
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Contributions

AB: Cell culture experiments, data curation & writing of the original draft. AGF Thottian: Sample collection & patient follow-up. GB: Sample collection, patient follow-up & writing of original draft, PK: Methodology & writing of the original draft.

Corresponding authors

Correspondence to K. Govind Babu or Prashant Kumar.

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The authors declare no potential conflicts of interest.

Ethical approval

This study was approved by the ethics committee of Kidwai Memorial Institute of Oncology, Bangalore, India. Moreover, informed consent has been obtained from all the patients included in the study. The authors declare that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent has been obtained from all the patients included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Figs. 2, 3 and 4 and Supplementary Table 1.

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Balakrishnan, A., Thottian, A.G.F., Govind Babu, K. et al. Drug susceptibility testing of circulating lung cancer cells for personalized treatment. Med Oncol 40, 1 (2023). https://doi.org/10.1007/s12032-022-01860-3

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