Cancer treatments can be particularly hard on children. But in the Infusionarium their minds are transported to mountain slopes where, depending on their tastes, they are surrounded by extreme skiers or Disney princesses.
Understanding Personalized Diagnostics
Each cancer can respond differently to treatment based on a patient’s genes. With the help of Penn’s Center for Personalized Diagnostics (CPD), patients and their oncologists can work together to better understand their situation and aim towards a safer, more effective treatment path.
No Two Cancers Are the Same
We understand that cancer is incredibly personal, affecting you or your loved ones on a variety of levels. That’s why our approach to your care is equally precise and personal. We look at individual risk factors, symptoms and treatment decisions that have already been made or considered; then we determine the most effective and least invasive form of treatment.
Cancer is also personal on another level—all the way down to our individual DNA.
Sometimes referred to as “the building blocks of life,” combinations of these 25,000 genes tell our cells which functions to perform and how to interact with one another. Genetic mutations can occur when there are errors, or imperfections, in our genes.
These mutations tell our cells to behave differently than they normally would, possibly causing tumors to grow and thrive. Additionally, they may cause abnormal reactions to traditional treatments like chemotherapy or radiation.
Oftentimes cancer patients are only aware that they carry a mutation once they have been diagnosed and have responded poorly to a common treatment. Penn’s Center for Personalized Diagnostics (CPD) aims to help patients and their doctors understand their genetic makeup early on, to make the most of their treatment.
The Benefits of a Personalized Genetic Profile
Rapid advances in technology and personalized diagnostics have made it possible to understand the genetic make-up of an individual tumor and the biochemical instructions it follows. Depending on the type and stage of the cancer, a regular biopsy or blood sample may be all your doctor needs to help.
Armed with this information, physicians, oncologists and genetic counselors have a much clearer picture of how your body and cancer interact.
An Ability to Customize Treatment
A genetic profile of cancer cells can show which specific mutations are causing a person’s individual cancer to spread.
Studying these genes allows pathologists, scientists and oncologists to better understand the intricate ways our bodies may react to different treatments.
Most important perhaps, a genetic profile can significantly reduce the time that conventional treatment approaches impose on the patient.
A Life-Changing Decision
Personalized diagnostics made a major difference for Mark and Kim. When he was diagnosed with stage 4 lung cancer, Mark thought he had no choice but to receive chemotherapy.
A genetic screening at Penn showed Mark that he actually carried a rare mutation that less than four percent of lung cancer patients carry. Thanks to his test, Mark and his oncologist found a clinical drug being tested specifically for that mutation. It quickly shrunk 80 percent of his tumor and turned his life around.
Acetylated Tubulin and Metastatic Potential in Breast Cancer
Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic potential in breast cancer. In suspended cell culture conditions, metastatic breast cancer cells exhibited high α-tubulin acetylation levels that extended along microtentacle (McTN) protrusions. Mutation of the acetylation site on α-tubulin and enzymatic modulation of this posttranslational modification exerted a significant impact on McTN frequency and the reattachment of suspended tumor cells. Reducing α-tubulin acetylation significantly inhibited migration but did not affect proliferation. In an analysis of more than 140 matched primary and metastatic tumors from patients, we found that acetylation was maintained and in many cases increased in lymph node metastases compared with primary tumors. Proteomic analysis of an independent cohort of more than 390 patient specimens further documented the relationship between increased α-tubulin acetylation and the aggressive behaviors of basal-like breast cancers, with a trend toward increased risk of disease progression and death in patients with high-intensity α-tubulin acetylation in primary tumors. Taken together, our results identify a tight correlation between acetylated α-tubulin levels and aggressive metastatic behavior in breast cancer, with potential implications for the definition of a simple prognostic biomarker in patients with breast cancer. Cancer Res; 75(1); 1–13. ©2014 AACR.
miR-490-3p Targets Oncogenic SMARCD1 in Gastric Cancer
Chromatin remodeling has emerged as a hallmark of gastric cancer, but the regulation of chromatin regulators other than genetic change is unknown. Helicobacter pylori causes epigenetic dysregulation to promote gastric carcinogenesis, but the roles and functions of microRNAs (miRNA) in this multistage cascade are not fully explored. In this study, miRNA expression in preneoplastic and neoplastic lesions in murine stomachs induced by H. pylori and N-methyl-N-nitrosourea (MNU) was profiled by miRNA expression array. miR-490-3p exhibited progressive downregulation in gastritis, intestinal metaplasia, and adenocarcinoma during H. pylori and MNU-induced gastric carcinogenesis. Significant downregulation of miR-490-3p was confirmed in human gastric cancer tissues in which its regulatory region was found to be hypermethylated. miR-490-3p exerted growth- and metastasis-suppressive effects on gastric cancer cells through directly targeting SMARCD1, a SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex subunit. Knockdown of SMARCD1 significantly attenuated the protumorigenic effects of miR-490-3p inhibitor, whereas enforced expression of SMARCD1 promoted in vitro and in vivo oncogenic phenotypes of gastric cancer cells. SMARCD1 was markedly upregulated in gastric cancer in which its high expression was associated with shortened patients’ survival independent of TNM staging. In conclusion, hypermethylation-mediated silencing of miR-490-3p reactivates SMARCD1 to confer malignant phenotypes, mechanistically linking H. pylori, chromatin remodeling, and gastric carcinogenesis. Cancer Res; 75(4); 1–12. ©2014 AACR.
Epigenetic silencing of miR-490-3p reactivates the chromatin remodeler SMARCD1 to promote Helicobacter pylori-induced gastric carcinogenesis
Chromatin remodeling has emerged as a hallmark of gastric cancer, but the regulation of chromatin regulators other than genetic change is unknown. Helicobacter pylori causes epigenetic dysregulation to promote gastric carcinogenesis, but the roles and functions of microRNAs (miRNAs) in this multi-stage cascade are not fully explored. In this study, miRNA expression in pre-neoplastic and neoplastic lesions in murine stomachs induced by H. pylori and N-methyl-N-nitrosourea (MNU) was profiled by miRNA expression array. MiR-490-3p exhibited progressive downregulation in gastritis, intestinal metaplasia and adenocarcinoma during H. pylori and MNU-induced gastric carcinogenesis. Significant downregulation of miR-490-3p was confirmed in human gastric cancer tissues in which its regulatory region was found to be hypermethylated. MiR-490-3p exerted growth- and metastasis-suppressive effects on gastric cancer cells through directly targeting SMARCD1, a SWI/SNF chromatin remodelling complex subunit. Knockdown of SMARCD1 significantly attenuated the pro-tumorigenic effects of miR-490-3p inhibitor whereas enforced expression of SMARCD1 promoted in-vitro and in-vivo oncogenic phenotypes of gastric cancer cells. SMARCD1 was markedly upregulated in gastric cancer where its high expression was associated with shortened patients’ survival independent of TNM staging. In conclusion, hypermethylation-mediated silencing of miR-490-3p reactivates SMARCD1 to confer malignant phenotypes, mechanistically linking H. pylori, chromatin remodeling and gastric carcinogenesis.
