2025-03-02

Genetic mutations and personalized treatment

This section is quite technical, but I include it to document everything as thoroughly as possible and because it presents some new data that affects my life expectancy.

Massive Sequencing (NGS)

Massive sequencing / next-generation sequencing (NGS, for its acronym in English) is used in colon cancer to:

• Identify mutations and genetic alterations: It allows the detection of variants in critical genes, helping to understand the tumor's biology.
• Personalize treatment: By knowing the cancer’s molecular profile, targeted therapies or more suitable treatments can be selected for each patient.
• Establish prognoses and therapeutic strategies: The genetic information obtained can be correlated with treatment response and disease progression.
• Discover new biomarkers: This facilitates early detection, monitoring, and research into mechanisms of therapy resistance.

In my case, sequencing was performed through a liquid biopsy since the tumor tissue biopsy extracted from the colon was not valid.

My sequencing results

Relevant biomarkers

Identified molecular variants

About KRAS A146T

Recurrent mutations in RAS oncogenes cause constitutive activation and are found in 20-30% of cancers. KRAS mutations are observed in 30-35% of lung adecnocacicoma and colorectal cancer. The majority of KRAS mutations consist of point mutations ocurring at G12, G13 and Q61. Mutations at A59, K117 and A146 have also been observed but are less frequent.

So, having A146T variant was about 1-2% probability.

What does having this variant mean?

From this study:

Results Most patients carried a KRAS G12 mutation (N = 112), followed by mutations in G13 (N = 15), A146 (N = 12), Q61 (N = 9), and K117 (N = 5). High plasma circulating tumor DNA levels were observed for patients carrying a KRAS A146 mutation versus those with a KRAS G12 mutation, with median mutant allele frequencies of 48% versus 19%, respectively. Radiologic TTV revealed this difference to be associated with a higher tumor load in patients harboring a KRAS A146 mutation (median TTV 672 cm3 [A146] v 74 cm3 [G12], P = .036). Moreover, KRAS A146 mutation carriers showed inferior overall survival compared with patients with mutations in KRAS G12 (median 10.7 v 26.4 months; hazard ratio = 2.5; P = .003).

Conclusion Patients with mCRC with a KRAS A146 mutation represent a distinct molecular subgroup of patients with higher tumor burden and worse clinical outcomes, who might benefit from more intensive treatments. These results highlight the importance of testing colorectal cancer for all KRAS mutations in routine clinical care.

Things are looking worse and worse, to be honest.

Specific Treatment

Once the variants have been identified, it seems that in the third round of chemotherapy, in addition to FOLFOX, an additional chemotherapy treatment called bevacizumab can be applied. When I asked the oncologist about it, they said its effectiveness/improvement was between 5-10%. Based on my research so far, this could be the case, but there are no specific studies on A146T in advanced stages like mine.

In this article, with the help of AI, I have compiled all the information I could find about A146T and its treatment.

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