Comprehensive Treatment Options

Personalized treatment recommendations based on DNA-sequencing a comprehensive cancer panel of 1091 genes providing insight on:

• Deep sequencing at 1,000x coverage to detect subclonal variants . Deep sequencing, typically ranging from 500x to 1,000x coverage, is often recommended for detecting subclonal variants in next-generation sequencing (NGS) data. Deep sequencing can lead to high:

  Sensitivity

  Precision

  Statistical power

  Reproducibility

  Sensitivity

  Sensitivity: Higher sequencing coverage increases the sensitivity of variant detection, allowing for the detection of low-frequency variants present in a small fraction of cells or subclones within a sample. This is particularly important for identifying subclonal variants, which may be present at lower allele frequencies compared to dominant or clonal variants.

  Precision

  Precision: Higher coverage also improves the precision of variant calling, reducing the false positive rate and increasing the accuracy of variant detection. This is important for minimizing false positives that can result from sequencing errors, mapping errors, or other technical artifacts.

  Statistical power

  Statistical power: Higher coverage increases the statistical power for detecting variants, particularly rare variants. It provides more robust evidence for the presence of a variant, which is particularly important when dealing with low-frequency subclonal variants that may be present in a small fraction of cells.

  Reproducibility

  Reproducibility: Higher coverage helps ensure the reproducibility of variant calling results across different samples, sequencing runs, or bioinformatics pipelines. It provides a more consistent and reliable basis for comparing variant calls across different datasets or studies.

• Variants with demonstrated therapeutic interventions
• Therapeutic interventions guided by somatic variants, such as targeted therapies, immunotherapies, hormonal therapies etc.
  • Targeted therapies: Certain somatic variants, such as mutations in specific genes or proteins, can be targeted with precision therapies. For example, tyrosine kinase inhibitors (TKIs) like imatinib, which targets the BCR-ABL fusion protein in chronic myeloid leukemia (CML), or vemurafenib, which targets the BRAF V600E mutation in melanoma, are examples of targeted therapies that are designed to specifically inhibit the activity of mutated proteins associated with cancer.
  • Immunotherapies Somatic variants can also influence the tumor microenvironment and immune response. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, which block the PD-1/PD-L1 pathway, have shown efficacy in various cancers with somatic variants that result in increased tumor mutational burden (TMB) or the presence of specific immune-related biomarkers.
  • Hormonal therapies: Somatic variants can affect hormonal signaling pathways, leading to targeted hormonal therapies. For example, in breast cancer somatic variants in the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) genes can guide the use of hormonal therapies such as tamoxifen, letrozole, or trastuzumab, respectively.
• HRD score calculation. HRD (Homologous Recombination Deficiency) is a measure to assess the presence of DNA repair deficiencies, specifically in the homologous recombination pathway. HRD score is typically calculated based on:
  • Loss of heterozygosity (LOH): LOH refers to the loss of one copy of a gene or a portion of a chromosome in a tumor.
  • Telomeric allelic imbalance (TAI): TAI measures the imbalance between the long and short arms of a chromosome. HRD score is typically represented as a numerical value. Higher HRD scores indicate a higher likelihood of homologous recombination deficiency in a tumor, which can have implications for cancer treatment decisions. For example, tumors with higher HRD scores may be more responsive to certain types of DNA-damaging chemotherapy or targeted therapies that exploit the tumor's DNA repair deficiencies.
• Depiction of cancer-relevant pathways: Several cancer-relevant pathways that been identified as potential targets for therapeutic intervention. These pathways play crucial roles in cancer development and progression, and targeting them with specific drugs or interventions may disrupt the cancer cells' ability to grow, divide, and survive.
  • PI3K/AKT/mTOR pathway: This pathway is involved in regulating cell growth, survival, and metabolism, and is often dysregulated in cancer. Inhibitors of PI3K, AKT, or mTOR have been developed as targeted therapies for various types of cancer, including breast cancer, lung cancer, and hematologic malignancies.
  • RAS/RAF/MEK/ERK pathway: This pathway plays a role in cell proliferation and survival, and is commonly mutated in many types of cancers, including colorectal cancer, lung cancer, and melanoma. Inhibitors targeting BRAF, MEK, or other components of this pathway have been developed as targeted therapies for cancers with RAS or BRAF mutations.
  • Epidermal Growth Factor Receptor (EGFR) pathway: This pathway is involved in cell growth and is frequently dysregulated in several cancers, such as lung cancer and colorectal cancer. EGFR inhibitors, such as tyrosine kinase inhibitors (TKIs), have been developed as targeted therapies for cancers with EGFR mutations.
  • DNA damage repair pathways: These pathways, including the homologous recombination (HR) pathway and the nucleotide excision repair (NER) pathway, are essential for maintaining genomic stability. Inhibitors targeting specific components of these pathways, such as PARP inhibitors for HR-deficient cancers, have been developed as targeted therapies for cancers with DNA repair defects, including breast cancer and ovarian cancer.
  • Immune checkpoint pathways: These pathways, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), are involved in regulating the immune response to cancer cells. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have been developed as immunotherapies for various cancers, including melanoma, lung cancer, and bladder cancer.
  • Angiogenesis pathway: This pathway involves the formation of new blood vessels to support tumor growth. Vascular endothelial growth factor (VEGF) inhibitors, such as bevacizumab, have been developed as targeted therapies to inhibit angiogenesis and are used in the treatment of several types of cancers, including colorectal cancer, lung cancer, and ovarian cancer
  • Wnt/β-catenin pathway: This pathway is involved in regulating cell proliferation and is frequently dysregulated in various cancers, including colorectal cancer and liver cancer. Inhibitors targeting specific components of this pathway, such as Wnt inhibitors or β-catenin inhibitors, are under investigation as potential targeted therapies.
• Amplifications and deletions . Amplifications and deletions are types of copy number variants (CNVs) that involve the duplication or deletion of genomic segments, respectively. These alterations in DNA copy number can have important implications for therapeutic intervention in various disease conditions.
  • Amplification of oncogenes, which are genes that promote cell growth and division, is a common occurrence in cancer. Therapeutic interventions can be designed to specifically target these amplified oncogenes, either by using targeted therapies that inhibit the activity of the oncogene or by directly targeting the amplified DNA segments using techniques like antisense oligonucleotides or small interfering RNA (siRNA).
  • Amplification of specific genes that are known drug targets can be leveraged for therapeutic intervention. For example, amplification of the human epidermal growth factor receptor 2 (HER2) gene in breast cancer is targeted by the drug trastuzumab, which specifically inhibits the overactive HER2 protein, leading to reduced cancer cell growth.
  • Deletions of tumor suppressor genes, which are genes that normally suppress cell growth and prevent tumor formation, can result in loss of their function and contribute to cancer development. Therapeutic interventions can be aimed at restoring the function of these deleted tumor suppressor genes, either by gene replacement strategies, such as gene editing using CRISPR-Cas9, or by using gene therapies that deliver functional copies of the missing gene into the cells.
  • Amplifications and deletions can also be targeted in combination with other therapeutic strategies. For example, targeted therapies that inhibit oncogene amplifications may be used in combination with chemotherapy or radiation therapy to achieve a synergistic effect and improve treatment outcomes.
• Comprehensive proprietary database of FDA approved/clinical trial drugs for corresponding biomarkers
• Analysis of 637 germline variants affecting drug metabolism
• Test available for all solid tumor and hematologic malignancies