China
Africa
Explore chapters and articles related to this topic
Familial Pancreatic Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Use of systemic preoperative non-adjuvant chemotherapy alone or in combination with radiotherapy for 3–6 months before undergoing surgery helps reduce the size of the tumor, increase the likelihood of negative resection margins, and tests the effects of cytotoxic medications in vivo. Following surgery, adjuvant chemotherapy with gemcitabine (also known as dFdC: 2′,2′-difluorodeoxycytidine, which remains a cornerstone treatment for all stages of PDAC) or 5-fluorouracil is recommended. FOLFIRINOX (fluorouracil, folic acid, irinotecan, and oxaliplatin; a platinum-based chemotherapy) and protein-bound paclitaxel (nab-paclitaxel) chemotherapy are more effective than gemcitabine but appear to cause significant side effects. Tumors harboring somatic or germline pathogenic variants in genes related to DNA double strand damage repair (e.g., BRCA1, BRCA2, PALB2, or ATM) show better responses to platinum-based chemotherapy [24–29].
Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Daniel Bobo, Kye J. Robinson, Jiaul Islam, Kristofer J. Thurecht, Simon R. Corrie
Protein nanoparticles span a number of different nanomedicine classes, from drugs conjugated to endogenous protein carriers to engineered proteins where the active therapeutic is the protein itself, and to combined complex platforms that rely on protein motifs for targeted therapeutic delivery. Early protein nanoparticles sought to use the natural properties of protein circulating in serum, allowing dissolution and transport of drug compounds in blood during circulation. This approach consisted of natural protein combined with known drugs in order to reduce toxicity. Abraxane® is an early example of protein-drug conjugation. Approved by the FDA in 2005, Abraxane® is albumin-bound paclitaxel in particle form designed to eliminate the need for the toxic solvent, Cremophor, normally required for paclitaxel delivery [57]. The 130 nm human serum albumin protein-bound paclitaxel particles improved infusion time and eliminated the need for coadministration of powerful antihistamines or dexamethasone in order to prevent immunoreaction to the Cremophor solvent (polyethoxylated castor oil). Beyond the initial goal of reducing toxicity, further study of Abraxane® has found improved pharmacokinetics and enhanced tumor inhibition when compared to the Cremophor-based therapy due to enhanced endothelial binding and transcytosis of the nanoparticle [58]. Abraxane® has exemplified protein-drug nanoparticles as excellent nanomaterials for improving toxicity and passive delivery to a desired target. As such, several albumin-bound nanoparticles (NABs) have been entered into clinical trials seeking to improve the therapeutic efficacy of other drugs. Examples include NAB-docetaxel, NAB-rapamycin, and NAB-heat shock protein inhibitor. Since its approval in 2005, there has been a shift from unmodified protein to the utilization of more highly engineered particle complexes in order to gain active targeting functionality.
The microbiome of pancreatic cancer: from molecular diagnostics to new therapeutic approaches to overcome chemoresistance caused by metabolic inactivation of gemcitabine
Published in Expert Review of Molecular Diagnostics, 2018
Arthur T.F. Choy, Ilaria Carnevale, Stefano Coppola, Laura L. Meijer, Geert Kazemier, Egija Zaura, Dongmei Deng, Elisa Giovannetti
Another important point that needs to be addressed is that some oral bacteria have been found to be associated with pancreatic cancer and some are known to be causative agents of the most common oral infections, periodontal diseases [14,16]. The association between periodontal diseases and pancreatic cancer has been reported in previous epidemiological studies [17,18]. Michaud and collaborators described that the levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were elevated in pancreatic cancer patients [19]. Interestingly, the results of the evaluated study indicate that these two oral pathogens contain CDDS and CDDL, respectively. This implies that they may also contribute to the resistance to gemcitabine in pancreatic cancer. Furthermore, a recent study has implicated P. gingivalis in mediating the chemoresistance to paclitaxel in patients with oral squamous cell carcinoma through a Notch1 dependent mechanism [20]. Since the next generation protein-bound paclitaxel, also known as nanoparticle albumin-bound paclitaxel (nab-paclitaxel), has become a standard treatment option (in combination with gemcitabine) for metastatic pancreatic cancer, further investigations are required in order to verify whether the activation of Notch1 by bacteria mechanisms could also influence chemoresistance in pancreatic cancer.
Nanocarrier-based co-delivery approaches of chemotherapeutics with natural P-glycoprotein inhibitors in the improvement of multidrug resistance cancer therapy
Published in Journal of Drug Targeting, 2022
Shadab Md, Nabil A. Alhakamy, Priyanka Sharma, Mohammad Shahnawaze Ansari, Bapi Gorain
The introduction of nanotechnology in the field of medicine has brought several serendipities in the evolution and expansion of novel medicines for the treatment of complex disease conditions. However, there are several characterisation parameters of the nanocarriers along with their in vivo behaviour for long-term use by the consumers should be understood for the safety and efficacy of the therapeutics before being commercialised [141]. With the increasing numbers of researches in the field of nanotechnology, researchers are targeting deliveries to combat the complex microenvironment of cancer as well as to combat the resistance stage [142]. Several novel delivery products have been commercialised for the treatment and diagnosis of different diseases, viz. DaunoXome (liposomal daunorubicin), Doxil/Caelyx (liposomal doxorubicin), Estrazorb (micellar nanoparticle of estradiol), Emend (nanocrystalline aprepitant), Abraxane (protein-bound paclitaxel nanoparticles), Resovist (iron nanoparticles), Acticoat (silver nanoparticles), etc. [143]. The process of translating these nanomedicines into commercialisation is supported by different funding agencies to combat the deadliest diseases safely, not only for the purpose of treatment but also for diagnosis and theranostic approaches [144]. There are 381 studies have been registered at www.clinicaltrials.gov to combat MDR, whereas 53 studies have been registered to evaluate the efficacy of P-gp in different cancer conditions. Out of the 53 studies, 10 studies are focussed on MDR to evaluate the effect of P-gp. All the studies on MDR with P-gp inhibitory effects in order to reverse resistance in cancer cells were conducted to establish the efficacy of synthetic P-gp inhibitors, particularly PSC 833 (valspodar), XR9576 (tariquidar), etc. These studies are focussed on the specific efficacy of the P-gp inhibitors without affecting other systems of the patients, including the microsomal enzyme system. In continuation to the previous discussion, non-interference to other systems and specificity towards the cancer microenvironment would not produce any toxic manifestation through damaging the integrity of different body systems or biological barriers. In addition, prolonged stay, site-specific internalisation into the cancer cells and controlled release of therapeutics would be expected from the novel carriers. Thus, proper evaluation of the pharmacokinetic and pharmacodynamic profile of the combination nano-deliveries will surely help reversing MDR and control cancer conditions with a significant reduction of the risks [145].