Pancreatic Cancer: Current Multimodality Treatment Options and the Future Impact of Molecular Biological Profiling

Abstract

<b><i>Background:</i></b> Pancreatic cancer (PDAC) – even if deemed resectable – has still a dismal prognosis and is the seventh leading cause of global cancer-related death with rising incidence worldwide. <b><i>Summary:</i></b> Surgical resection at best in combination with adjuvant systemic chemotherapy is the only potentially curative treatment. Surgical treatment has substantially improved over the last years with significantly reduced perioperative morbidity and mortality. Even when deemed radiologically resectable, the majority of PDAC is likely to have micrometastases, leaving most PDAC patients with an advanced stage. Recent 5-year overall survival was up to 46% in patients eligible for surgery with intensified adjuvant chemotherapy. Eligible for curative surgery are about one-third of the patients, and only 20% of these patients have the option for cure with surgery and adjuvant chemotherapy. Standards of care in treating PDAC patients include various mostly combinational chemotherapy approaches in the advanced and adjuvant setting. Moreover, first targeted therapies for individualizing treatment, e.g., specific subgroups like BRCA1/2 germline mutated patients, were established lately. Neoadjuvant concepts are currently part of research. This review focuses on current and future multimodal treatment options of PDAC and the impact of molecular profiling for individualizing treatment. <b><i>Key Messages:</i></b> State of the art in pancreatic cancer therapy is multimodal and includes novel strategies to allow molecular defined subgroup-specific treatment.

Anti-Cancer SERCA Inhibitors Targeting Sorafenib-Resistant Human Papillary Thyroid Carcinoma

“…The stemness and aggressiveness of refractory PTC have not yet been revealed. Outcomes from the advancement of anti-cancer drugs finding many studies have described that pre-operative chemotherapy can extend the survival rates after surgery [ 44 , 45 , 46 , 47 ]. Nonetheless, no selective therapeutic options have been accepted as the basal adjuvant or neoadjuvant background for drug-resistant cancer [ 48 , 49 , 50 ], and a substantial number of anti-cancer drug-resistant cancer patients have died; therefore, unmet medical needs have consistently increased.…”

Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma

“…Owing to the development of anti-cancer drugs, numerous studies have reported that preoperative chemotherapy improves the survival rates after surgery and demonstrated the effect of properly administered chemotherapy and performed surgery even when effective treatment was considered impossible [ 25 , 26 , 27 , 28 ]. Nevertheless, no treatment options have been accepted as the standard neoadjuvant or adjuvant setting for HCC [ 29 , 30 , 31 ], and considerable numbers of HCC patients with cancer died; therefore, unmet medical needs have steadily increased.…”

“…By ECBS, chemical pairs are considered as “similar” when their binding targets are identical or evolutionarily related. Among variants of ECBS models, the target-specific ensemble ECBS (TS-ensECBS) model was adapted for the virtual screening owing to the highest test accuracy in our previous study [ 26 ]. The TS-ensECBS model was built for SERCA (i.e., the ERCPs are only defined for SERCA and its homologous proteins).…”

Potential Therapeutic Agents against Paclitaxel—And Sorafenib-Resistant Papillary Thyroid Carcinoma

“…Anticancer drug discovery has evolved and new therapeutic strategies against cancer have emerged. Thus, preoperative chemotherapy expands survival rates after surgery, and adequate chemotherapy and surgery are effective even in unfavorable clinical situations [ 43 , 44 , 45 , 46 ]. However, there are no effective therapeutic options for the management of antineoplastic-resistant cancer [ 47 , 48 ].…”