Two-Drug Combination Shows Promise Against One Type of Pancreatic Cancer

“One form of pancreatic cancer has a new enemy: a two-drug combination discovered by UF Health researchers that inhibits tumors and kills cancer cells in mouse models.

“For the first time, researchers have shown that a certain protein becomes overabundant in pancreatic neuroendocrine tumors, allowing them to thrive. They also found that pairing a  with an existing drug provides a more effective anticancer punch than a single drug. The findings were published recently in the Journal of the National Cancer Institute by a group that includes Rony A. François, an M.D./Ph.D. student working with Maria Zajac-Kaye, Ph.D., an associate professor in the UF College of Medicine’s department of anatomy and cell biology.

“Finding new treatments is critical because less than 5 percent of patients with pancreatic neuroendocrine tumors respond to everolimus, the most commonly used pharmaceutical, François said. Neuroendocrine tumors, which form in the hormone-making , account for 3 percent to 5 percent of pancreatic malignancies and have a five-year survival rate of about 42 percent, according to the National Cancer Institute. Pancreatic neuroendocrine tumors are increasingly common, which medical experts and researches have attributed to better diagnostic imaging, an aging population and heightened awareness of the disease stemming from the 2011 death of Apple Inc. co-founder Steve Jobs.”


New Gene Discovered that Stops the Spread of Deadly Cancer

The gist: Oncologists can sometimes test a tumor biopsy from a patient to see if the tumor has certain mutations that can be targeted by specific drugs. New research has uncovered a tumor mutation—deletion of the gene DIXDC1—that could play a role in treatment decisions for people with non-small cell lung cancer (NSCLC). Patients with DIXDC1 deletion or deletion of another gene called LKB1 might benefit from drugs known as FAK inhibitors. (Both DIXDC1 and LKB1 play a role in suppressing metastasis, so when they are missing, it may be easier for lung cancer tumors to spread to other parts of the body.) Further research is needed to investigate whether DIXDC1 and LKB1 deletion could be used to help with treatment decisions.

“Scientists at the Salk Institute have identified a gene responsible for stopping the movement of cancer from the lungs to other parts of the body, indicating a new way to fight one of the world’s deadliest cancers.

“By identifying the cause of this metastasis—which often happens quickly in and results in a bleak survival rate—Salk scientists are able to explain why some tumors are more prone to spreading than others. The newly discovered pathway, detailed today in Molecular Cell, may also help researchers understand and treat the spread of melanoma and cervical cancers.

” ‘Lung , even when it’s discovered early, is often able to metastasize almost immediately and take hold throughout the body,’ says Reuben J. Shaw, Salk professor of molecular and cell biology and a Howard Hughes Medical Institute early career scientist. ‘The reason behind why some tumors do that and others don’t has not been very well understood. Now, through this work, we are beginning to understand why some subsets of lung cancer are so invasive.’ “


MEK Inhibition Affects STAT3 Signaling and Invasion in Human Melanoma Cell Lines

“Elevated activity of the mitogen-activated protein kinase (MAPK) signaling cascade is found in the majority of human melanomas and is known to regulate proliferation, survival and invasion. Current targeted therapies focus on decreasing the activity of this pathway; however, we do not fully understand how these therapies impact tumor biology, especially given that melanoma is a heterogeneous disease. Using a three-dimensional (3D), collagen-embedded spheroid melanoma model, we observed that MEK and BRAF inhibitors can increase the invasive potential of ∼20% of human melanoma cell lines…”


HIF1α and HIF2α independently activate SRC to promote melanoma metastases

Malignant melanoma is characterized by a propensity for early lymphatic and hematogenous spread. The hypoxia-inducible factor (HIF) family of transcription factors is upregulated in melanoma by key oncogenic drivers. HIFs promote the activation of genes involved in cancer initiation, progression, and metastases. Hypoxia has been shown to enhance the invasiveness and metastatic potential of tumor cells by regulating the genes involved in the breakdown of the ECM as well as genes that control motility and adhesion of tumor cells…”