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Management of Individuals Living with Blood Cancer

The past half century has witnessed an impressive understanding of cancer in general, and the cancer genome in particular, not just in hematological malignancies, but in diverse cancers. We also firmly recognize the relationship between the cancer cell and its normal tissue microenvironment, and the interplay between this microenvironment and the immune system and the broader concept of inflammation. We now know that about 20 percent of human cancers are related to chronic inflammationi caused by diverse factors, such as autoimmune disease, irritants and infections, such as Helicobacter pylori infections in a subtype of gastric lymphoma. As our understanding of the underlying molecular biology, the cancer ecosystem and cancer-related inflammation improves, we are beginning to appreciate the complexity of the diverse processes and their profound effects on the tissue microenvironment and the malignant clone.

Though the first targeted cancer medicine was probably tamoxifen for patients with breast cancer, it was really the introduction of imatinib (Gleevec®) in 1998 for the treatment of individuals with a rare form of blood cancer, called chronic myeloid leukemia or CML, which is generally credited for ushering in the precision medicine era. The lessons learned from treating these patients have led to the development and availability of targeted medicines for numerous cancers, and remarkably, as cancer cells evolve and develop resistance to therapies, new lessons are garnered from these patients with CML which help overcome many of the resistance mechanisms in play. In tandem, molecular technologies have evolved rapidly and we have witnessed the emergence of comprehensive genomic profiling tests. By way of illustration, analytical and clinical validation of two comprehensive genomic profiling assays, FoundationOne® and FoundationOne® Heme, have been reported recently to detect all currently recognized classes of molecular aberrations. Many global cancer experts now recognize the ability of assays like these to accord favorable diagnostic and prognostic evaluation2 and in many cases, the results of these assays are able to predict clinical outcomes aligned with suitable therapies3-5. For example, FoundationOne® Heme was recently used in a study to profile 3,696 patients with hematological cancers, including acute myeloid leukemia, multiple myeloma and lymphomas, both Hodgkin and non-Hodgkin. The study observed that 77 percent of the blood cancers harbored at least one molecular alteration linked to a molecularly targeted therapy, either licensed or in clinical development6. FoundationOne® Heme is also expanding the frontiers of comprehensive genomic profiling by identification of the genomic landscape, and the keynote drivers of cancer progression in blood cancers7-10.

The month of September is a time to recognize the profound impact that blood cancer has had on so many individuals around the world. September should also be a month to reflect upon the great progress that has been made towards developing innovative targeted therapies, and to remind us all of the collective imperative to integrate a molecular information / precision medicine approach to the treatment of individuals with blood cancer.

Notes
  1. De Marzo AM et al. (2007) Inflammation in prostate carcinogenesis. Nature Reviews Cancer. 7:256-269.
  2. Sidransky D. (2002) Emerging molecular markers of cancer. Nature Reviews Cancer. 2:210-219.
  3. Rizvi et al. (2015) Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348(6230):124-128.
  4. Rosenberg et al. (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 387(10031):1909-1920.
  5. Snyder et al. (2014) Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. New England Journal of Medicine. 371:2189-2199.
  6. He, J. et al. (2016) Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting. Blood. 127(24):3004-14.
  7. Ley T. et al. (2008) DNA sequencing of a cytogenetically normal acute myeloid leukemia genome. Nature. 456:66–72.
  8. Sonu, RJ et al. (2015) Optimal Molecular Methods in Detecting p190 (BCR-ABL) Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature. Case Rep Hematol. 2015:458052.
  9. Chalmers, ZR et al. (2015) Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy. Blood Cancer J. 5, e278.
  10. Kasi, PM et al. (2016) Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets. Leuk Res Rep. 5:7–10.