Familial Pancreatic Carcinoma

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

BRCA2, PALB2, CDKN2A, PALLD, BRCA1, RABL3, SMAD4, KRAS, TP53, ATM, H3P10, PALD1, MSH6, PKHD1, FANCG, SUB1, H3P8, GTF2H5, CD47, IDO2, MAGT1, CDH10, SF3B6, LAMTOR2, CDK2, CDKN1A, CHEK2, RPP14, CDK2AP2, FANCC

Drugs

(1-methyl-2-nitro-1H-imidazole-5-yl)methyl N,N'-bis(2-bromoethyl) diamidophosphate, 2-hydroxy-N,N,N-trimethylethan-1-aminium (Z)-4-(5-((3-benzyl-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoate, 26 base single stranded phosphodiester DNA oligonucleotide, 3-bromopyruvate, 4-amino-1-[(1S,4R,5S)-2-fluoro-4,5-dihydroxy-3-(hydroxymethyl) cyclopent-2-en-1-yl] pyrimidin-2-one, 4-imino-1, 3-diazobicyclo-[3.1.0]-hexan-2-one, 5'-O-(trans-9''-octadecenoyl)-1-beta-D-2'deoxy-2',2'-difluorocytidine, 5,10-methylene-tetrahydrofolic acid, 5-10-Methylene-tetrahydrofolate, Adenoviral vector of serotype 5 modified to contain a chimeric sequence consisting of a minimal urokinase-type plasminogen activator receptor promoter preceded by three Notch-responsive elements, and coated with oligopeptide end-modified poly (beta-amino) esters, Algenpantucel-L, Antroquinonol, Autologous human adipose perivascular stromal cells genetically modified to secrete soluble tumour necrosis factor-related apoptosis-inducing ligand, Axitinib ( INLYTA ), Bevacizumab ( Equidacent, AVASTIN, Aybintio, MVASI ), Bovine bile extract, Brivudine, Cetuximab ( ERBITUX ), Chimeric antibody to mesothelin, Chimeric monoclonal antibody against claudin-18 splice variant 2, Cisplatin (liposomal), Cysteamine bitartrate ( CYSTAGON ), Cytochrome P450 isoform 2B1 gene transfected human embryonic kidney 293 cells encapsulated in polymeric cellulose sulphate, Demcizumab, Deuterium oxide, Devimistat, Eryaspase ( GRASPA ), G17(9) gastrin-diphtheria toxoid conjugate, GVAX, Genetically modified human adenovirus encoding human PH20 hyaluronidase, Glufosfamide, Heat killed whole cell mycobacterium obuense, Heparan sulfate mimetic, Herpes simplex type 1 virus containing cellular B-myb gene as tumour-specific promoter, Human telomerase reverse transcriptase peptide (611-626), Human trtravalent, bi-specific monoclonal antibody that binds and co-inhibits two growth factor receptors; insulin-like growth factor receptor 1 (IGF-1R) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3), Humanised IgG4 monoclonal antibody to the human toll-like receptor type 2, Humanized IgG monoclonal antibody hRS7 conjugated to topoisomerase I inhibitor, Imexon, Immunoglobulin G1, anti-(human tumour-associated calcium signal transducer 2)(human-Mus musculus monoclonal hRS7 heavy chain), disulfide with human-Mus musculus monoclonal hRS7 ê-chain, dimer, hexakis(thioether) with (4S)-4-[[[[4-[[(2S)-2-(4-aminobutyl)-2-[[2-[2-[[26-[4-[[[[4-[(3-mercapto-2,5-dioxo-1-pyrrolidinyl)methyl]cyclohexyl][...][3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, Iodine (131I) anti-CEA sheep-human chimeric monoclonal antibody, Live attenuated Listeria monocytogenes delta actA/delta inlB strain expressing human mesothelin, Masitinib mesilate, Mixture of seven synthetic fragments consisting of p21 RAS peptides, Modified adenovirus serotype 5/35 containing a CMV promoter-driven transgene cassette with the human transgenes for a membrane-bound CD40 ligand and full length 4-1BBL, N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]isonicotinamide hydrochloride, N1,N14,-diethyl-3,12,-dihydroxyhomospermine, Nanoliposomal irinotecan ( ONIVYDE ), Nimotuzumab ( THERALOC ), PEGylated recombinant human hyaluronidase PH20, Paclitaxel (liposomal), Paclitaxel protein-bound particles ( ABRAXANE ), Pegylated recombinant human interleukin-10, Polyinosine-polycytidylic acid coupled with the polycationic polyethyleneimine, Re188 P2045 somatostatin analog, Recombinant human monoclonal antibody of the IgG1 kappa class against prostate stem cell antigen, Relacorilant, Rubitecan, S-[2,3-bispalmitoyloxy-(2R)-propyl]-cysteinyl-GNNDESNISFKEK, Salirasib, Targeted Gastrin 17 Complexed Peptide, Trabedersen, Trastuzumab ( HERCEPTIN ), Yttrium (90Y)-DOTA-radiolabelled humanized monoclonal antibody against mucin 1, [5-amino-1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxy-propoxy)-phenyl]-methanone, human reovirus type 3 Dearing strain, motixafortide, sodium 2-hydroxylinoleate

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Familial pancreatic carcinoma is defined by the presence of pancreatic cancer (PC) in two or more first-degree relatives.

Epidemiology

The annual incidence has been estimated at approximately 1-10/1,000,000, representing 5-10% of all PC cases.

Clinical description

In familial cases, disease onset occurs before 50 years of age, earlier than for the other forms of PC. A high incidence of familial PC has been observed within hereditary syndromes (Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma syndrome, hereditary breast and ovarian cancer syndrome, and hereditary nonpolyposis colorectal cancer; see these terms). Smoking represents a significant risk factor associated with familial PC. PC can arise from the exocrine (95%) or endocrine portions of the pancreas. In 60% of cases it occurs within the head of the pancreas. The main symptoms are non-specific and include pain in the upper abdomen that typically radiates to the back, loss of appetite, significant weight loss and painless jaundice due to bile duct obstruction. As the clinical course is silent, PC often goes undetected until the advanced stages of the disease. In more than 80% of cases, the cancer is either locally advanced or disseminated at the time of diagnosis. A rapid growth pattern, early vascular dissemination, spread to regional lymph nodes, and metastases to distant organs (liver, peritoneum, lungs) are characteristic. PC can also invade the surrounding visceral organs.

Etiology

Mutations in the KRAS, CDKN2A, TP53, and SMAD4 genes have been shown to play a role in the etiology of PC. However, they are still not clinically useful for screening or for diagnosing the disease.

Diagnostic methods

Diagnostic methods include ultrasound, contrast-enhanced multidetector computed tomography (MDCT); magnetic resonance (MR) imaging, and integrated positron emission tomography (PET)/computed tomography (CT). Invasive diagnostic techniques are endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound. CA 19-9 is a sensitive tumor serum marker but is not specific.

Differential diagnosis

Differential diagnoses include a wide variety of diseases such as acute and chronic pancreatitis, cholangitis, cholecystitis, cholelithiasis, bile duct tumors and strictures, and gastric cancer and ulcers.

Management and treatment

Surgical resection is the only potentially curative treatment. However, most patients (80%) present with advanced non-resectable tumors. In these cases, chemotherapy (gemcitabine) or radiotherapy, alone or in combination, are alternative treatments, although rather ineffective.

Prognosis

Prognosis is poor (with an overall 5-year survival rate of 5%). Even after complete resection of the tumor, recurrence rates remain high. Patients with a family history of PC should be strongly advised to avoid or cease smoking.