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Case Study 06 – Head and Neck Cancer

Patient: 54 years – Male diagnosed with Squamous cell carcinoma of Buccal Mucosa

Clinical Testing:

  • Alterations: G12A, I774Nfs3, R280K, Q331, R979W, K722Rfs14, R552
  • Gene: HRAS, ATR, TP53, TERT, RAD50, PPM1D

Treatment Options: Overall preclinical and clinical data suggests that the use of DDR inhibitors alone or in combination with other therapies, such as radiotherapy or chemotherapy is promising, for the treatment of HNSCC (Lei, Huimin et al.2022)

Indication: This is the case of Adenocarcinoma Lung with symptomatic brain metastasis.

Research Findings: HRAS is altered in 3.51% of head and neck squamous cell carcinoma patients. According to COSMIC data (Oct 2022), 5.6% cases had HRAS mutations in both squamous and non-squamous carcinomas of the upper aerodigestive tract. Loss-of-function genes involved in the homologous recombination repair pathway (ATR & RAD50) can sensitize tumors to PARP inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. Somatic missense mutations in TP53 gene implicates chemoresistance. Studies have reported that presence of promoter TERT mutations may alter the TERT levels and telomere erosion in patients with HNSCC (Boscolo-Rizzo, Paolo et al.2020)y more resistant to chemotherapy and radiation.

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