One may try to determine whether a breast cancer has bad prognosis in order to determine whether chemotherapy should be given (MammaPrint, Oncotypr DX), but more importantly, I believe, is to focus on genes of good prognosis which include driver genes against which we dispose of an answer in our Arsenal.
Currently we dispose of
1. Chemotherapy that attacks DNA and Microfilament/Microtubules, (first and second law of nature)
2. Immune Modulators such as Interferon
3. Antibody to Membrane Receptor (EGFR/VEGF) Avastin
4. Inhibitor to T-cell driven immunity (CTLA4)
5. Inhibitors to sub-membrane or first line driver Mutations KRAS, HRAS, or the RAS family
6. Inhibitors to 2nd line driver Mutations (anti MEK)
7. Inhibitor to Tertiary line driver Mutations and Mitochondrial level inhibition (MTOR, Metformin)
8. Anti-proteasome or inhibitor to cellular protein degradation (Velcade)
9. Inhibitors at Nuclear lever Include Histone Deacethylator and Acyl transferase inhibitor, check point controller inhibitors, anti-Centrosome metabolism and inhibitors of various promoters and transcription factors.
Other opportunities not included in this classification go to specific genes of proliferation, Amplification, differentiation and metastasis that have been brought forth as indicator of either response to chemotherapy or simply as "Good prognosis" genes. These will include the BRCA since a response to PARP inhibitors and Cisplatin based combinations should be anticipated.
Multikinase inhibitors such as Dasatinib (SRC+ BCR/ABL but also STAT5) and Arsenic Trioxide should be included
LBK1: could predict early disease (inhibitor controlling initiation of metastasis)
DDR2: could predict anti MEK sensitivity
MEKK-1 sensitivity to Cisplatin
TFF1-could predict sensitivity to estrogen despite negative Estrogen
DYRK2, favorable in lung cancer
c-JUN amplification and over expression of 8q23-24 could predict response to interferon/Interleukin
EGFR, VEGF, ALK, and other Driver Mutations would match those discussed By DR Kris in lung cancer.
(to be continued!)
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