Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. Cancer Res; 74(13); 1–9. ©2014 AACR.

Prostate cancer is frequently characterized by a large inflammatory infiltrate that includes T cells. Although T cells traffic to cancer lesions in large numbers, they are unable to generate a therapeutic response because of the immunosuppressive microenvironment. Therefore, arming T cells with a cytotoxic agent that is capable of killing cancer cells independent of these immunosuppressive signals is a rational approach to enhance their potency. Essentially, the T cells would serve as a cell-based vector, or “Trojan Horse,” to selectively deliver a protoxin to disseminated prostate cancer lesions. The selective delivery of a protoxin using T cells represents an ideal method to maximize their therapeutic potency through a “field effect.” Because systemically infused T cells are expected to traffic to sites of inflammation other than cancer, an additional level of specificity may be needed to prevent toxicity to nontarget tissues. Toward this goal, genetic engineering can be used to make protoxin expression dependent upon T-cell recognition of the prostate-specific membrane antigen by a chimeric antigen receptor. Furthermore, selective activation of the protoxin using a tissue- or tumor-specific protease, such as PSA, can promote further specificity. Thus, T-cell potency can be enhanced by targeted protoxin secretion and greater specificity achieved using combinatorial antigen recognition and protoxin activation. Cancer Res; 74(13); 1–6. ©2014 AACR.

We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the observed mutation profiles. Samples were derived from three cohorts: Cohort 1 consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post-NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations who became negative for the mutations after NCT had a higher Miller–Payne score (P = 0.008), improved disease-free survival, and improved overall survival than those with no change or the opposite change. The association of loss of mutations in TP53 and PIK3CA and improved survival was successfully validated in the second cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with or without the mutations. Our data reveal the novel concept that chemotherapy may reduce mutation frequency in patients with breast cancer. Furthermore, the loss of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for prognosis via further verification, which may optimize the choice of sequential therapy and improve patient survival. Cancer Res; 74(13); 1–9. ©2014 AACR.

Glioblastoma multiforme (GBM) is one of the most aggressive human brain malignancies. Even with optimal treatment, median survival is less than 6 months for patients with recurrent GBM. Immune-based therapies have the potential to improve patient outcome by supplementing standard treatment. Expression of human cytomegalovirus (CMV) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy. Here, we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T-cell therapy as a consolidative treatment for recurrent GBM. From a total of 19 patients with recurrent GBM, CMV-specific T cells were successfully expanded from 13 patients (68.4%), 11 of whom received up to four T-cell infusions. Combination therapy based on T-cell infusion and chemotherapy was well tolerated, and we detected only minor adverse events. The overall survival of these patients since first recurrence ranged from 133 to 2,428 days, with a median overall survival of 403 days. Most importantly, 4 of 10 patients that completed the treatment remained progression free during the study period. Furthermore, molecular profiling of CMV-specific T-cell therapy from these patients revealed distinct gene expression signatures, which correlated with their clinical response. Our study suggests that a combination therapy with autologous CMV-specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for patients with recurrent GBM. Cancer Res; 74(13); 1–11. ©2014 AACR.

Integrative medicine and wellness services are offered at the Abramson Cancer Center. Reiki, yoga and acupuncture can supplement traditional cancer treatments – leading to a better quality of life by reducing the side effects of cancer and treatments. Adam Schreiber, acupuncturist for Penn Medicine’s Integrative Medicine program, explains the advantages of the procedure for cancer patients. Adam SchreiberAdam Schreiber is an experienced acupuncturist licensed by the Pennsylvania State Board of Medicine and certified in Oriental Medicine by the National Certification Commission for Acupuncture and Oriental Medicine.Adam has worked with the director of Penn Medicine’s Integrative Medicine and Wellness program, Jun Mao, MD in National Institutes of Health-funded clinical trials of acupuncture, for pain and symptom management in breast cancer, for the last three years.Well regarded by patients and colleagues as highly professional, compassionate, and skillful, Adam is the first credentialed non-physician acupuncturist to join Penn Medicine.What is acupuncture? Acupuncture originated in China, and has been practiced for more than 2,500 years. It is a technique in which hair-thin needles are inserted through the skin to treat a variety of conditions.While it is not fully understood, the mechanism through which acupuncture can help pain and symptom distress may involve helping the brain to release neuro-chemicals such as endorphins and helping the brain to better regulate regulate the autonomic nervous system. Through these and other mechanisms of action, acupuncture can help combat the side effects of cancer and aggressive cancer treatment.How does an acupuncture session work?During a typical acupuncture session, patients lay comfortably on a cushioned table. An acupuncturist then inserts hair-thin, single-use sterilized needles into the patient’s skin in key areas, known to stimulate the body to help heal itself.Sessions typically lasts between 20 and 40 minutes, depending on the treatment plan for the individual patient.Schreiber adds, “most patients tolerate the procedure with minimal discomfort – it’s not at all like having blood drawn, or receiving a vaccination”. Sometimes patients can see results immediately, and sometimes it may take several sessions before any benefit can be realized. Generally speaking, patients will know if acupuncture can help them within four to eight treatments.How can acupuncture supplement my cancer treatment options and survivorship efforts?”One of the reasons I like working with cancer patients,” says Schreiber, “is because [acupuncture] compliments all the other treatments Penn Medicine is already doing very well. Some of these treatments are really aggressive, and can cause problems outside of their intended effects, like chemotherapy. Acupuncture can help alleviate those side effects – it works with the body’s natural ability to heal itself.”Why come to Penn Medicine for acupuncture instead of a neighborhood practice?Penn’s Integrative Medicine and Wellness program is designed with the cancer patient in mind. It brings acupuncture directly into a conventional cancer therapy setting and treatment is tailored specifically to the patient’s needs. Our doctors and researchers are also hard at work conducting research to better understand how acupuncture intersects with cancer treatment, which will help us to understand how acupuncture can best help each individual patient.“I think that’s what’s nice about it,” said Schreiber, “knowing you’re going to an acupuncturist that is comfortable [and experienced] with these types of patients, one who sees them regularly and understands their concerns.”Scheduling an AppointmentFor more information, or to schedule a visit, please call 215-615-5858, extension #4.Acupuncture services are located on the 4th floor West Pavilion of the Ruth and Raymond Perelman Center for Advanced Medicine.