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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

Lynparza The results of a phase III trial presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) show that the Lynparza PARP inhibitor delays cancer progression and improves survival when used to treat BRCA-mutated pancreatic cancer and is the first precision cancer medicine to become available for the treatment of pancreatic cancer.

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer. All patients should undergo genomic biomarker testing for these and other markers.1,2

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.3

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.4

Larotrectinib (LOXO-101) 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.5

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.6,7

References


1 Pancreatic Cancer Action. Facts and statistics. Accessed February 2019 from https://pancreaticcanceraction.org/about-pancreatic-cancer/medical-professionals/stats-facts/facts-and-statistics/

2 news.cancerconnect.com/pancreatic-cancer/lynparza-first-promising-new-drug-to-treat-pancreatic-cancer-in-years-H6BzHID6FUiWnbz7R-Oe8A/

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

4 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.

5 https://news.cancerconnect.com/rectal-cancer/larotrectinib-demonstrates-76-percent-response-rate-in-trk-fusion-cancers-h0SNZscax0q60J_w9hZKBA/

6 Abbruzzese JL, Rosenberg A, Xiong Q, LoBuglio A, et al. Phase II study of anti-epidermal growth factor receptor (EGFR) antibody cetuximab (IMC-C225) in combination with gemcitabine in patients with advanced pancreatic cancer. Proceedings from the 37th Annual Meeting of the American Society of Clinical Oncologists 2001, San Francisco CA, Abstract #518.

7 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.

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