Precision Cancer Medicine

for Pancreatic Cancer

There is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with the same type of cancer, the behavior of the cancer and its response to treatment can vary widely. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment. It is becoming increasingly clear that specific characteristics of cancer cells and cancer patients can have a profound impact on prognosis and treatment outcome. Although factoring these characteristics into treatment decisions makes cancer care more complex, it also offers the promise of improved outcomes.

Not all cancer cells are alike

Cancer cells may differ from one another based on what genes have mutations.  Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome.  This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy”

Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.

Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

Precision cancer medicines can be used both instead of and in addition to chemotherapy to improve treatment outcomes.

Precision Cancer Medicines for Pancreatic Cancer

Pamrevlumab (FG-3019) is a monoclonal antibody that inhibits connective tissue growth factor (CTGF), which is associated with pancreatic cancer and growth of abnormal stromal cells and tumor cells. Pamrevlumab has received Breakthrough Therapy Designation from the FDA and when used in combination with chemotherapy appears to improve responses in locally advanced pancreatic cancer compared to chemotherapy alone.1

Herceptin® (trastuzumab); is a currently available precision cancer medicine that binds to the HER2 receptor, (a protein on the surface of the cancer cells) in approximately 20% of patients with pancreatic cancer. This binding action promotes anticancer benefits through two distinct processes. First, the binding of Herceptin blocks growth factors from binding to HER2, thereby eliminating their stimulating effects on cancer cells. Second, the binding action of Herceptin appears to stimulate the immune system to attack and kill the cancer cells to which Herceptin is bound. Herceptin when combined with chemotherapy for treatment of patients that overexpress HER2 prolongs survival compared to treatment with chemotherapy alone.2

Larotrectinib (LOXO-101) has received Breakthrough Therapy Designation from the FDA for the treatment of advanced solid tumors with NTRK-fusion proteins. Larotrectinib targets a mutation where two genes join together in what’s known as tropomyosin receptor kinases (TRK) fusion, leading to the production of proteins that cause cancer growth. Growing research suggests that the TRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.3

Targeting ras:  More than 85% of pancreatic cancers have mutations in the ras gene; these malignant cells contain a unique enzyme (known as farnesyl transferase) whose activity appears to be required if the cells with the mutation are to divide. Specific drugs that inhibit farnesyl transferase have been developed and are being evaluated in clinical trials. Similarly, methods are being explored through which the normal (rather than mutated) gene can be directly injected into a tumor mass with the hope that a return to the usual pattern of cell division will lead to tumor regression.4

Erbitux® (cetuximab); is a precision cancer medicine that binds to epidermal growth factor receptors (EGFR), thereby suppressing cancer growth and spread. The addition of Erbitux to chemotherapy may modestly improve survival for patients with advanced pancreatic cancer.2,5

Next: Radiation Therapy for Pancreatic Cancer

References


1 http://news.cancerconnect.com/preliminary-results-suggest-that-pamrevlumab-is-promising-in-pancreatic-cancer/

2 Safran H, Ramanathan R, Schwartz J, King T, et al. Herceptin and Gemcitabine for Metastatic Pancreatic Cancers That Overexpress her-2/neu. Proceedings from the 37th Annual Meeting of the American Society of Clinical Oncology 2001, San Francisco CA, Abstract #517.

3 Cascinu S, Berardi R, Labianca R, et al. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, Phase II trial. Lancet Oncology. 2008;9:39-44.

4 Toubaji A, Achtar M, Provenzano M et al. Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers.Cancer Immunol Immunother. 2008 Feb 23.

5 http://news.cancerconnect.com/larotrectinib-demonstrates-76-percent-response-rate-trk-fusion-cancers-including-pancreatic-cancer/