2023-10-22 15:59:41
Title: Biomarker Discovered to Predict Chemotherapy Resistance and Relapses in Colorectal Cancer
Subtitle: Study sheds light on how DPPA3 factor influences chemoresistance and disease relapse
Date: [Insert Date]
Colorectal cancer is a global health concern, with millions of new cases and deaths reported annually. A groundbreaking study conducted by scientists at the Vall d’Hebron Institute of Oncology (VHIO) has identified a promising biomarker that could predict chemoresistance and relapses in patients with colorectal cancer.
Chemotherapy resistance is a major obstacle in the effective treatment of colorectal cancer. It is often caused by the interruption of the cell cycle in tumor cells, allowing them to evade cell death triggered by therapy. This non-mutational mechanism not only grants tumors the ability to resist chemotherapy but also increases the risk of disease relapse, even years after treatment.
In their study, led by scientist Héctor G. Palmer, the researchers focused on discovering new mechanisms that regulate disease progression and acquired resistance. They found that the overexpression of the DPPA3 factor, also known as Developmental Pluripotency Associated 3, is a major regulator of “slow cyclicity” and chemoresistance in colorectal cancer.
By examining samples from patients with primary and metastatic colorectal cancer, the researchers observed a correlation between high DPPA3 concentration and the likelihood of disease recurrence. Importantly, this overexpression was found to be indicative of a relapse caused by cellular plasticity rather than genetic changes.
The researchers considered two potential strategies to control recurrences. Firstly, they hypothesized that blocking DPPA3 during chemotherapy could prevent cells from entering a quiescent state and maintain their sensitivity to therapy. Secondly, maintaining DPPA3 overexpression after treatment could prevent quiescent cells from re-entering the cell cycle and triggering relapse.
However, developing a direct inhibitor for the disordered structure of the DPPA3 factor proved challenging. Instead, the team explored the vulnerabilities of cells expressing DPPA3 to identify potential indirect interventions. They discovered that the hypoxia-DPPA3 axis, a feedback loop involving elevated levels of the key hypoxia regulator HIF1, enabled tumor cells to remain in a quiescent state and acquire resistance to chemotherapy.
The study’s findings highlight the predictive value of DPPA3 overexpression for chemoresistance and disease relapse in colorectal cancer patients. Furthermore, the researchers identified HIF1 as a potential therapeutic target to deactivate the quiescent state of colon cancer cells and sensitize them to chemotherapy.
Moving forward, the researchers plan to use their cell models to explore additional approaches to break the vicious circle between DPPA3 and HIF1. By evaluating the effectiveness of combining DPPA3-HIF1 inhibition with chemotherapy in animal models, the team aims to enhance chemotherapy effectiveness and minimize relapse risk.
While more research and preclinical evaluations are required, these findings offer new insights into the mechanisms underlying chemoresistance in colorectal cancer. They pave the way for the development of innovative strategies to combat this widespread disease, potentially improving patient outcomes and reducing mortality rates.
This study, which represents a significant step forward in the fight against colorectal cancer, was published in the journal Cell Reports.
**Note: This news article is based on a press release from the Vall d’Hebron Institute of Oncology. The original publication can be found [here].**]
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