To do this we likely have to integrate AI. Patients usually aren't trained in oncology. And our medical oncologists are burdened with a substantial workload already.
One thing I would add to the profile is:
Labs: DEXA, PSA, testosterone, DHT, SHBG, etc.
I upload 15+ documents to AIs for background. One of them is a rough profile document:
Diagnosed in 2018 with Gleason 4+5 T3b/T4 N1M0 SVI, Positive margins, bladder wall invasion.
I am mHSPC GG5 no DNA mutations and I do not have metabolic syndrome. My glucose and insulin levels are low/moderate. I am lean and muscular. Very little bodyfat. All analysis should assume that. I used to have mets but they were eradicated with SBRT in 2023.
6/23/2025 PSA 0.17. Testosterone 232 ng/dl – PSA is overexpressed by androgens. PSADT = N/A (same today as it was when I started aBAT 4 years ago). PSAV = 0.0 ng/mL/Month
Signatera ctDNA MRD 0.0
My goals include: eradication of CSCs, control of mets and eradiation of micro-mets, maintaining HSPC status (avoid CRPC), reduction of MRD (Signatera), athletics.
Molecular profiling of my primary tumor revealed two somatic loss-of-function mutations in the KMT2D gene—a stop-gain variant and a frameshift mutation. These alterations likely compromise KMT2D’s normal function in maintaining genomic stability through epigenetic regulation, rather than directly affecting DNA repair mechanisms. Consequently, tumors deficient in KMT2D may be particularly sensitive to PARP inhibitors, such as olaparib, due to compensatory vulnerabilities within their DNA damage response OSNs. However, the implications for bipolar androgen therapy (BAT) are less clear, since BAT primarily modulates androgen receptor signaling and does not directly intersect with the OSNs affected by KMT2D alterations.
Feature KMT2D Mutations BRCA1/2 or ATM Mutations
Primary Role Epigenetic regulator (histone H3K4 methylation) DNA damage repair (homologous recombination repair, HRR)
Molecular Impact Disrupts enhancer regions, impairing transcriptional regulation of oncogenic OSNs (e.g., PI3K/Akt, EMT) Disrupt DNA repair, leading to genomic instability and accumulation of driver mutations
DNA Repair Link Indirect: Loss increases ROS via FOXO3 suppression, sensitizing cells to DNA damage Direct: Loss of HRR causes synthetic lethality with PARP inhibitors
DNA Variant Table (all of these variants were on the chip)
Important to realize that these are SNPs, not somatic or germline variants.
Gene/Marker Variant/rsID Genotype/Status Estimated Detection Accuracy Mechanistic Theory Evidence Weighting Clinical Significance BAT Relevance
BRCA1 rs189382442 & rs552911643 T/T (biallelic) 25-50% BRCA1 inactivation → HRD → impaired DSB repair → synthetic lethality with BAT + PARPi (A). A
(NCT03522064) Loss-of-function mutations lead to homologous recombination deficiency (HRD), rendering tumors more vulnerable to DNA damage. High sensitivity to BAT-induced DNA damage; enhances synergy with PARP inhibitors.
BRCA2 rs276174802 Loss-of-function 30-60% BRCA2 loss → HRD → BAT-induced replication stress + PARPi → cell death (A). A
(NCT03522064) Biallelic inactivation results in HRD, increasing replication stress and double-strand breaks (DSBs) upon treatment. HRD tumors are highly sensitive to BAT, and this state synergizes with PARP inhibitors (e.g., olaparib).
TP53 rs78378222 (and others, e.g., rs1800372) T/T (pathogenic) 80%-95%(multiple variants detected) TP53 loss → defective DNA repair → BAT amplifies DSBs; PARPi prevents repair (B/C). B/C (COMBAT Trial) Impaired DNA repair that may amplify BAT-induced DNA damage, though associated with a more aggressive cancer phenotype. Enhances the therapeutic window for BAT—especially when combined with PARP inhibitors—by further compromising DNA repair.
AR rs201097725 C/C 95%-98% Enhanced AR signaling under SPA → BAT-induced growth arrest (B/C). B/C (TRANSFORMER Trial) Variants may enhance AR signaling under supraphysiologic androgen (SPA) pulses, potentially increasing susceptibility to growth arrest induced by BAT. High AR dependency generally predicts a good BAT response, though resistance may emerge through AR downregulation.
ATM rs1800056 T/T (homozygous) 40%-60% ATM kinase inactivation → HRD-like state → BAT + PARPi exploit replication stress (B/C). C (Preclinical) A truncating mutation (p.Arg35Ter) leading to ATM loss-of-function, classified as pathogenic per ClinVar. A strong predictor of synergy when combining BAT with PARP inhibitors due to impaired double-strand break repair.
ATM rs587779826 T/T (homozygous) 40%-60% ATM kinase inactivation → HRD-like state → BAT + PARPi exploit replication stress (B/C). C (Preclinical) Likely pathogenic missense variant disrupting ATM kinase activity, also compromising the DNA repair process. Enhances synthetic lethality when BAT-induced DNA damage is paired with PARP inhibition.
No prob. Just put in what you're comfortable with. Mine is just an example of what I use - not the best, hopefully not the worst.
Most of the genomic mutation and SNP stuff I got from either test reports or from AI. AI eventually "forgets" things so I keep what I think are the most important things in summary files for it.
I like the way you think.
To do this we likely have to integrate AI. Patients usually aren't trained in oncology. And our medical oncologists are burdened with a substantial workload already.
One thing I would add to the profile is:
Labs: DEXA, PSA, testosterone, DHT, SHBG, etc.
I upload 15+ documents to AIs for background. One of them is a rough profile document:
Diagnosed in 2018 with Gleason 4+5 T3b/T4 N1M0 SVI, Positive margins, bladder wall invasion.
I am mHSPC GG5 no DNA mutations and I do not have metabolic syndrome. My glucose and insulin levels are low/moderate. I am lean and muscular. Very little bodyfat. All analysis should assume that. I used to have mets but they were eradicated with SBRT in 2023.
6/23/2025 PSA 0.17. Testosterone 232 ng/dl – PSA is overexpressed by androgens. PSADT = N/A (same today as it was when I started aBAT 4 years ago). PSAV = 0.0 ng/mL/Month
Signatera ctDNA MRD 0.0
My goals include: eradication of CSCs, control of mets and eradiation of micro-mets, maintaining HSPC status (avoid CRPC), reduction of MRD (Signatera), athletics.
Molecular profiling of my primary tumor revealed two somatic loss-of-function mutations in the KMT2D gene—a stop-gain variant and a frameshift mutation. These alterations likely compromise KMT2D’s normal function in maintaining genomic stability through epigenetic regulation, rather than directly affecting DNA repair mechanisms. Consequently, tumors deficient in KMT2D may be particularly sensitive to PARP inhibitors, such as olaparib, due to compensatory vulnerabilities within their DNA damage response OSNs. However, the implications for bipolar androgen therapy (BAT) are less clear, since BAT primarily modulates androgen receptor signaling and does not directly intersect with the OSNs affected by KMT2D alterations.
Feature KMT2D Mutations BRCA1/2 or ATM Mutations
Primary Role Epigenetic regulator (histone H3K4 methylation) DNA damage repair (homologous recombination repair, HRR)
Molecular Impact Disrupts enhancer regions, impairing transcriptional regulation of oncogenic OSNs (e.g., PI3K/Akt, EMT) Disrupt DNA repair, leading to genomic instability and accumulation of driver mutations
DNA Repair Link Indirect: Loss increases ROS via FOXO3 suppression, sensitizing cells to DNA damage Direct: Loss of HRR causes synthetic lethality with PARP inhibitors
Therapeutic Targets PARP inhibitors (via ROS-mediated synthetic lethality), PI3K/Akt inhibitors PARP inhibitors (FDA-approved for BRCA1/2), platinum chemotherapy
I have the following SNPs profile:
DNA Variant Table (all of these variants were on the chip)
Important to realize that these are SNPs, not somatic or germline variants.
Gene/Marker Variant/rsID Genotype/Status Estimated Detection Accuracy Mechanistic Theory Evidence Weighting Clinical Significance BAT Relevance
BRCA1 rs189382442 & rs552911643 T/T (biallelic) 25-50% BRCA1 inactivation → HRD → impaired DSB repair → synthetic lethality with BAT + PARPi (A). A
(NCT03522064) Loss-of-function mutations lead to homologous recombination deficiency (HRD), rendering tumors more vulnerable to DNA damage. High sensitivity to BAT-induced DNA damage; enhances synergy with PARP inhibitors.
BRCA2 rs276174802 Loss-of-function 30-60% BRCA2 loss → HRD → BAT-induced replication stress + PARPi → cell death (A). A
(NCT03522064) Biallelic inactivation results in HRD, increasing replication stress and double-strand breaks (DSBs) upon treatment. HRD tumors are highly sensitive to BAT, and this state synergizes with PARP inhibitors (e.g., olaparib).
TP53 rs78378222 (and others, e.g., rs1800372) T/T (pathogenic) 80%-95%(multiple variants detected) TP53 loss → defective DNA repair → BAT amplifies DSBs; PARPi prevents repair (B/C). B/C (COMBAT Trial) Impaired DNA repair that may amplify BAT-induced DNA damage, though associated with a more aggressive cancer phenotype. Enhances the therapeutic window for BAT—especially when combined with PARP inhibitors—by further compromising DNA repair.
AR rs201097725 C/C 95%-98% Enhanced AR signaling under SPA → BAT-induced growth arrest (B/C). B/C (TRANSFORMER Trial) Variants may enhance AR signaling under supraphysiologic androgen (SPA) pulses, potentially increasing susceptibility to growth arrest induced by BAT. High AR dependency generally predicts a good BAT response, though resistance may emerge through AR downregulation.
ATM rs1800056 T/T (homozygous) 40%-60% ATM kinase inactivation → HRD-like state → BAT + PARPi exploit replication stress (B/C). C (Preclinical) A truncating mutation (p.Arg35Ter) leading to ATM loss-of-function, classified as pathogenic per ClinVar. A strong predictor of synergy when combining BAT with PARP inhibitors due to impaired double-strand break repair.
ATM rs587779826 T/T (homozygous) 40%-60% ATM kinase inactivation → HRD-like state → BAT + PARPi exploit replication stress (B/C). C (Preclinical) Likely pathogenic missense variant disrupting ATM kinase activity, also compromising the DNA repair process. Enhances synthetic lethality when BAT-induced DNA damage is paired with PARP inhibition.
ML met indicator: low risk
ML HSPC->CRPC indicator: very low risk
Waaayyyy over my head.
No prob. Just put in what you're comfortable with. Mine is just an example of what I use - not the best, hopefully not the worst.
Most of the genomic mutation and SNP stuff I got from either test reports or from AI. AI eventually "forgets" things so I keep what I think are the most important things in summary files for it.