Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 317-328 http://medscipublisher.com/index.php/cge 321 left-sided tumors. This differentiation is critical for determining the appropriate therapeutic approach (Osumi et al., 2018; Messaritakis et al., 2023). 4.2 Prognostic value Genetic mutations serve as powerful prognostic markers, providing valuable information on disease progression and patient outcomes. 4.2.1 Predicting disease progression Mutations in genes such as TP53 and KRAS are associated with more aggressive tumor behavior and poor prognosis. These mutations can predict disease progression, helping clinicians to stratify patients according to risk and tailor treatment plans accordingly. The presence of multiple driver mutations, such as in TP53 and APC, often indicates a higher risk of recurrence and metastasis (Raskov et al., 2019). 4.2.2 Personalized treatment plans The use of genetic mutation profiles allows for the development of personalized treatment plans that are tailored to the unique genetic makeup of a patient's tumor. For example, patients with KRAS mutations are typically resistant to anti-EGFR therapies, and this information is crucial for guiding treatment decisions. Personalized treatment approaches based on genetic profiles have been shown to improve patient outcomes and reduce treatment-related toxicity (Dimberg et al., 2020; Johnson et al., 2022). 4.3 Therapeutic targets Targeting specific genetic mutations in CRC has led to the development of effective therapies that improve patient survival and quality of life. 4.3.1 Targeted therapies based on genetic profiles Targeted therapies have become a cornerstone of CRC treatment, particularly for patients with actionable genetic mutations such as those in KRAS, BRAF, and PIK3CA. The identification of these mutations through genetic profiling allows for the selection of appropriate targeted therapies, such as BRAF inhibitors for patients with BRAF V600E mutations, leading to better clinical outcomes (Cao et al., 2019; Li et al., 2019). 4.3.2 Case study: success story of targeted therapy in CRC patient A notable case study demonstrated the success of targeted therapy in a patient with metastatic CRC who harbored a BRAF V600E mutation. The patient was treated with a combination of BRAF and MEK inhibitors, resulting in significant tumor regression and prolonged progression-free survival. This case highlights the potential of personalized medicine in transforming CRC treatment outcomes (Kato et al., 2019). 5 Genetic Mutations and Resistance to Therapy Resistance to therapy in colorectal cancer (CRC) is a significant challenge that limits the effectiveness of both traditional chemotherapies and targeted therapies. Understanding the genetic and molecular mechanisms underlying resistance can provide insights into developing strategies to overcome it. 5.1 Mechanisms of resistance Therapy resistance in CRC is often driven by complex mechanisms, including secondary mutations and epigenetic changes that alter tumor cell behavior and survival. 5.1.1 Secondary mutations Secondary mutations are genetic alterations that occur in tumor cells after initial treatment, contributing to acquired resistance. For example, mutations in genes like KRAS and BRAF often emerge following anti-EGFR therapy, leading to resistance and tumor progression (Figure 2). These secondary mutations can bypass the targeted pathways, allowing cancer cells to survive despite therapy (Cao et al., 2020; Yamada et al., 2020). 5.1.2 Epigenetic changes Epigenetic modifications, such as DNA methylation and histone modification, play a critical role in the development of resistance to therapy in CRC. These changes can alter gene expression without changing the DNA
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