Whole exome sequencing uncovers HRAS mutations as potential mediators of resistance to metronomic chemotherapy

Sambath, Janani; Noronha, Vanita; Manda, Srikanth S.; Mishra, Rohit; Chandrani, Pratik; Patil, Vijay; Menon, Nandini; Chougule, Anuradha; Ramachandran, Venkatraman; Limaye, Sewanti; Kuriakose, Moni A.; Banavali, Shripad D.; Kumar, Prashant; Prabhash, Kumar

doi:10.1016/j.gene.2023.147952

Cited by 4 publications

(1 citation statement)

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“…Recent studies found molecular genetic markers or histologies associated with resistance to metronomic chemotherapy in head and neck cancer or triple-negative breast cancer [ 60 , 61 ]. These data might not be directly transferable to tissue editing approaches.…”

Section: Tissue Editing Approaches: Impact On the Genomic Evolution O...mentioning

confidence: 99%

Addressing Genetic Tumor Heterogeneity, Post-Therapy Metastatic Spread, Cancer Repopulation, and Development of Acquired Tumor Cell Resistance

Harrer,

Lüke,

Pukrop

et al. 2023

Cancers

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The concept of post-therapy metastatic spread, cancer repopulation and acquired tumor cell resistance (M-CRAC) rationalizes tumor progression because of tumor cell heterogeneity arising from post-therapy genetic damage and subsequent tissue repair mechanisms. Therapeutic strategies designed to specifically address M-CRAC involve tissue editing approaches, such as low-dose metronomic chemotherapy and the use of transcriptional modulators with or without targeted therapies. Notably, tumor tissue editing holds the potential to treat patients, who are refractory to or relapsing (r/r) after conventional chemotherapy, which is usually based on administering a maximum tolerable dose of a cytostatic drugs. Clinical trials enrolling patients with r/r malignancies, e.g., non-small cell lung cancer, Hodgkin’s lymphoma, Langerhans cell histiocytosis and acute myelocytic leukemia, indicate that tissue editing approaches could yield tangible clinical benefit. In contrast to conventional chemotherapy or state-of-the-art precision medicine, tissue editing employs a multi-pronged approach targeting important drivers of M-CRAC across various tumor entities, thereby, simultaneously engaging tumor cell differentiation, immunomodulation, and inflammation control. In this review, we highlight the M-CRAC concept as a major factor in resistance to conventional cancer therapies and discusses tissue editing as a potential treatment.

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Section: Tissue Editing Approaches: Impact On the Genomic Evolution O...mentioning

confidence: 99%