New Treatment Options in Metastatic Pancreatic Cancer

Fudalej, Marta; Kwaśniewska, Daria; Nurzyński, Paweł; Badowska-Kozakiewicz, Anna M.; Mękal, Dominika; Czerw, Aleksandra; Sygit, Katarzyna; Deptała, Andrzej

doi:10.3390/cancers15082327

Cited by 7 publications

(7 citation statements)

References 141 publications

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“…Various cocktail chemo-drugs with or without adjuvant therapy for PDAC patients have been intensely tested and studied 54 , 55 . This study proved a specific sonoporation setting using PDNSC that can reduce tumor hypoxia and enhance the efficacy of doxorubicin and gemcitabine for pancreatic tumors.…”

Section: Discussionmentioning

confidence: 99%

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors

Wu,

Wang,

Kang

et al. 2024

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.

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Section: Discussionmentioning

confidence: 99%

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors

Wu,

Wang,

Kang

et al. 2024

Sci Rep

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“…On the other hand, another ARB, losartan, reduced stromal collagen and hyaluronan production in PC models and, as a result, increased vascular perfusion and drug delivery [5]. Currently, losartan is under investigation in several PC clinical trials, including the combination of losartan with mFOLFIRINOX and beam proton radiation or the combination of losartan with gemcitabine (NCT01821729, NCT01276613).…”

Section: Discussionmentioning

confidence: 99%

“…Other factors influencing survival include early distant metastases, resistance to conventional treatment schemes, and a highly desmoplastic tumor microenvironment. Pancreatic cancer treatment options remain limited, as no immunotherapeutic or anti-angiogenic regimens have been approved [5]. If possible, the current approach encompasses multidisciplinary treatment with surgery, chemotherapy, and chemoradiotherapy [6].…”

Section: Introductionmentioning

confidence: 99%

The prevalence and impact of overweight and hypertension among patients with pancreatic cancer

Fudalej,

Cichowska,

Badowska-Kozakiewicz

et al. 2024

Oncol Clin Pract

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Introduction. Pancreatic cancer (PC) remains one of the most deadly malignancies with rising incidence. As therapeutical options seem unsatisfactory, great effort should be put into identifying and reducing risk factors as well as distinguishing possible factors influencing patient outcomes. The study aimed to describe the prevalence of overweight and hypertension among PC patients, analyse the possible association between overweight, hypertension and clinicopathological factors and distinguish variables influencing survival. Material and methods. A retrospective analysis of medical records was performed. The study was designed in two branches: (1) the comparison of patients with hypertension (HTN group) and without;(2) the comparison of patients with BMI ≥ 25 and patients with BMI < 25. Statistical analysis with the usage of appropriate tests was conducted. Results. No differences in survival between studied groups in the two branches were determined, even after subdividing into adjuvant and palliative types of treatment. Patients with HTN were more likely to be older, have diabetes and be diagnosed without distant metastases. BMI, ACEIs/ARBs use, diabetes, CRP/lymphocyte ratio (CLR) and AJCC IIb stage influenced survival. Patients with overweight/obesity were more likely to have an autoimmune disease, metastases in ≥ 4 lymph nodes (N2), tumour size between 2 and 4 cm (T2) and experience neutropenia as side effect of palliative chemotherapy. Higher BMI and CRP level influenced survival. Conclusions. The exact effect of ACEIs/ARBs on cancerogenesis should be further studied. CLR appears to be a feasible marker for prognosis in PC.

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“…In this regard, erlotinib has been used as an EGFR tyrosine kinase inhibitor. In 2005, the FDA approved erlotinib in combination with gemcitabine as a first-line treatment in locally advanced and metastatic PDAC [315]. It made no distinctions between KRAS conditions.…”

Section: Egfrmentioning

confidence: 99%

Genetic Signature of Human Pancreatic Cancer and Personalized Targeting

Reshkin,

Cardone,

Koltai

2024

Cells

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Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11–12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.

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New Treatment Options in Metastatic Pancreatic Cancer

Cited by 7 publications

References 141 publications

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors

The prevalence and impact of overweight and hypertension among patients with pancreatic cancer

Genetic Signature of Human Pancreatic Cancer and Personalized Targeting

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