Category Archives: Genetics

Monoclonal antibodies + kinase inhibitors are better than antibodies alone in breast cancer and B-cell lymphoma

The combination of Herceptin plus pan-HER (EGFR and Her 2 an 4) kinase inhibitor neratinib resulted in a 33% improvement in progression free survival versus Herceptin alone in breast cancer patients.  Rituxan combined with idelalisib, PI3K inhibitor, resulted in a near doubling of progression-free survival at 24 weeks versus Rituxan, alone in patients with Chronic Lymphocytic Leukemia, non-Hodgkin’s Lymphoma, and small cell lymphoma.  The news for neratinib tripled the valuation of Puma Biotechnology, while the FDA granted approval of Gilead’s drug Zydelig (idelalisib). Continue reading →

Cancer diagnostics in clinical use

Diagnostics that not only diagnose cancer, but also help select the appropriate therapy and monitor response are a mainstay in modern oncology, and their use is growing.  Precision medicine, identifying genetic markers of disease and designing treatments to exploit these, is the essence of  targeted cancer therapy.   Continue reading →

Ras – targeting the “undruggable”

The Ras onogene has been studied for 30 years, with over 40,000 scientific articles published on it.  However, an inhibitor of the mutated form of Ras has not been able to be developed.  So, researchers have developed downstream blockers of the Ras cascade – MEK inhibitors and Raf inhibitors, for example.  But why can’t a molecule that blocks mutated Ras be identified? Continue reading →

Beleodaq, a new pan-HDAC inhibitor approved for peripheral T-cell lymphoma

HDAC inhibitors work by blocking Histone De-ACetylase enzyme, which removes acetyl groups from the proteins that encase DNA, that is histones.  They are triggered by CpG sequences on DNA promoters; HDACs put chromatin in a configuration that favors LACK of transcription.  So, blocking HDACs favors transcription – see prior post.  Continue reading →

EGFRm+ non-small cell lung cancer – new treatments in development

For patients with activating mutations to the EGFR receptor kinase, small molecule specific inhibitors Iressa (gefintinib) or Tarceva (erlotinib) are administered as front-line treatments.  But, non-small cell lung cancers develop resistance after about one year of treatment via a single recurrent missense mutation (T790M) to the tyrosine kinase.  This is similar to resistance observed in patients with CML (Chronic Myeloid Leukemia) following treatment Gleevec (imatinib), which is mediated by a mutation to the Bcr-Abl transgene. Continue reading →

Epigenetic signature in blood for breast cancer risk

As reported in Genomic Medicine on June 27, an epigenetic signature in patients with BRCA1 and BRCA2 mutations was found by examining DNA methylation (DNAme) patterns on whole blood samples.  Importantly, this signature predicted for a high risk of developing breast cancer even in those patients who did NOT have BRCA1 and BRCA2 mutations. Continue reading →

PARP inhibitor rejected by FDA Advisory Committee, then Approved for refractory patients

In June 2014, the FDA Oncology Drug Advisory Committee voted 11-2 to delay approval of AstraZeneca’s olaparib, a PARP (poly-ADP ribose polymerase) inhibitor for maintenance therapy in patients with ovarian cancer.  The product received Accelerate Approval designation from the FDA, which provides for conditional approval pending follow-up studies, based on surrogate endpoints from Phase 2 trials, in this case, progression-free survival (PFS).  Continue reading →

Genetic Analyses of Cancer – Precision Medicine a New Standard

Memorial Sloan Kettering has started testing the cancers of its patients for 341 cancer-related genes.  It is collaborating with Quest Diagnostics to perform the analyses in an effort to identify biomarkers that can best guide appropriate therapy.  This is precision medicine, and it is happening at other major cancer centers, as well… Continue reading →

HPV DNA Test and Experimental DNA Vaccine

The National Cancer Institute states that “virtually all” cervical cancers are caused by HPV infection.  The association is so strong that the FDA recently approved a DNA test for HPV that many believe could supplant PAP smear.  This is great news for patients who do not have cervical cancer, yet.  But what if you do?… Continue reading →

Precision Medicine: SWOG Lung-MAP study – unique public/private collaboration

Using genomics to take-on advanced non-small cell lung cancer, the Southwest Oncology Group announced the start of a master protocol that will screen patients for optimal eligibility into one of five clinical trials with experimental drugs… Continue reading →