Revealing Drug Resistance Mechanisms in Tongue Cancer Using Organoids

Tongue cancer (TC) is the most common subtype of oral cancer characterized by an incidence of more than 300,000 new cases every year globally. Although TC patients with high risk are typically treated with surgery, followed by chemoradiotherapy, the recurrence rate remains high due to the existence of minimal residual disease (MRD). Rather, these findings yield insight into the formation of MRD and their relation to treatment efficacy which is valuable for enhancing future treatment results (1^✔ ✔Trusted Source
Host metabolism balances microbial regulation of bile acid signalling

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Challenges with Traditional Preclinical Models

Cancer cell lines are currently the principal in vitro models used in cancer research and drug discovery. However, these models have limitations:

• Some of the issues associated with the process of getting cell lines to grow from primary tissues.
• Lack of ability to faithfully represent the characteristics of the tumor for the given patient.

This variability makes it challenging to establish individual solutions for the treatment of TC.

Adoption of Tongue Cancer Organoids

In order to overcome these challenges, a research team came up with a patient-derived organoid library. To construct this extensive TCO library, researchers obtained fresh tissue biopsies from 28 untreated tongue cancer patients with a diverse age and cancer stage range.

As an organoid is a three-dimensional tissue model, the possibility of studying MRD formation and drug resistance in a controlled in-vitro environment represents a major advantage of harnessing this model.

Key Findings on Chemoresistance Mechanisms

The study revealed critical insights into MRD formation and chemoresistance:

• Dormant-like state in chemo-resistant TCOs: The researchers noticed what was akin to embryonic diapause where normal development is paused and cells rest.
• Role of autophagy and cholesterol biosynthesis: Chemoresistant TCOs had to depend on these pathways for their survival.
• Reversibility of chemoresistance: Blockade of autophagy and the synthesis of cholesterol promoted the selective elimination of chemo-resistant TCOs into chemo-sensitive TCOs. On the other hand, activation of autophagy gave chemoresistance.

The research highlights the potential of the TCO library as a resource for:

• Molecular target and biomarkers for chemoresistance.
• High efficiency through treatment customization according to patient characteristics.

The use of TCOs offers a methodological advance in the analysis of chemoresistance in tongue cancer. One of the significant merits of the study is that it reveals the pathways of autophagy and cholesterol biosynthesis that provide significance for inventing new therapeutic interventions and enhancing the prognosis of patients with difficult oral cancer. Additional actions in this regard are likely to yield further progress in the development of individualized treatments and the improvement of treatment outcomes.

Reference:

1. Host metabolism balances microbial regulation of bile acid signalling - (https://www.sciencedirect.com/science/article/abs/pii/S1534580724006075?)

Source-Medindia