Pancreatic Cancer Immuno-oncology in the Era of Precision Medicine
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REVIEW ARTICLE
Pancreatic Cancer Immuno-oncology in the Era of Precision Medicine Samarth Hegde 1 Received: 31 March 2020 / Accepted: 19 August 2020 # Indian Association of Surgical Oncology 2020
Abstract Pancreatic malignancies carry a dismal prognosis globally, with pancreatic adenocarcinomas (PDAC) being particularly aggressive and stubborn. Unfortunately, several therapeutic strategies that show promise in other cancers have failed to make sizeable impact on pancreatic tumor outcomes. Responses to immunotherapies are especially rare in pancreatic cancer, and patients are in need of innovative approaches that can result in more durable responses. Current research in preclinical models and humans has suggested this resistance is due to a uniquely inflammatory and dysfunctional tumor microenvironment; these findings lay the groundwork for targeting these barriers and improving outcomes. Clinical analyses have also revealed unprecedented heterogeneity in tumor and stromal biology of PDAC, underscoring the need for more personalized approaches and combinatorial therapies. This review will highlight the current state of translational research focusing on PDAC immunity, summarize ongoing clinical efforts to tackle PDAC vulnerabilities, and underscore some unresolved challenges in implementing therapies more broadly. A better understanding of immune contexture and tumor heterogeneity in this disease will greatly accelerate drug discovery and implementation of precision medicine for PDAC. Keywords Pancreatic cancer . Immunotherapy . Oncology . Cancer . Precision therapy . Targeted therapy
Pancreatic Cancer—an Introduction Pancreatic cancer ranks amongst the most common cancer types but also is the 4th leading cause of cancer-related deaths globally. Incidence rates vary between developing and developed countries, but pancreatic cancer is projected to outpace several malignancies (liver, colorectal, breast, prostate) over the next decade [1]. Incidences of pancreatic cancer will continue to rise due to increasingly Western lifestyle choices and prevalence of risk factors/comorbidities such as diabetes, idiopathic pancreatitis, obesity, smoking, and alcohol intake. Indeed, recent estimates suggest > 15,000 new Indian pancreatic cancer cases by 2021 [2]. It hence becomes important to revisit the cardinal features of this stubborn disease, recognize the features that make it challenging to treat immunologically, and review state-of-the-art immunotherapy-adjacent research. Doing so will enable physicians, oncologists, and researchers to collectively tackle key vulnerabilities in PDAC and develop future therapeutic strategies.
This review will focus on current translational landscape of PDAC immune-oncology; the reader is directed to extensive reviews that expand upon several of these topics [3–5]. Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of exocrine pancreatic cancer and the focus of this review. PDAC predominantly develops from three kinds of precursor lesions—intraepithelial neoplasia, intraducta
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