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Combination Therapy Development for Pancreatic Cancer
At Alfa Cytology, we are committed to advancing the fight against pancreatic cancer through the preclinical development of combination therapies. We focus on designing and optimizing therapeutic regimens combining multiple treatment modalities to enhance efficacy, reduce resistance, and improve patient outcomes. As a leading preclinical CRO, we offer a comprehensive range of services to support the development of innovative combination therapies tailored specifically for pancreatic cancer.
Overview of Combination Therapy Development for Pancreatic Cancer
Pancreatic cancer remains one of the most lethal forms of cancer, characterized by its aggressive nature, resistance to conventional therapies, and poor prognosis. Due to the complex biology of pancreatic tumors, monotherapy approaches often fall short of achieving durable responses. This has led to the increasing exploration of combination therapies, which aim to target multiple pathways and mechanisms involved in tumor growth and survival. By combining different therapeutic agents—such as chemotherapy, targeted therapy, immunotherapy, and oncolytic viral therapy—researchers seek to overcome treatment resistance and improve clinical outcomes.
Fig. 1 Cancer therapeutic approaches in combination with vaccination (Soltani M, et al., 2022)
Combination therapies leverage the synergistic effects of different treatment modalities to enhance overall therapeutic efficacy. For example, combining chemotherapeutic agents with immunotherapy can boost the immune system's ability to recognize and destroy cancer cells while reducing the tumor's capacity to evade immune surveillance. Similarly, pairing targeted therapies with oncolytic viral therapy can disrupt key survival pathways in cancer cells while simultaneously inducing direct cytotoxic effects. The potential of combination therapies in pancreatic cancer treatment lies in their ability to address the multifaceted nature of the disease, offering a more robust approach to therapy.
| Combination Therapy | Mechanism of Action |
|---|---|
| Curcuminoids + Chemotherapy | Upregulate Nrf2, enhancing anti-oxidative response and chemopreventive properties. |
| Resveratrol + Other Agents | Activates Nrf2, increasing GSH expression and anti-oxidative, chemopreventive effects. |
| Sulforaphane (SFN) + Taxol | Disrupts Nrf2-Keap1 complex, leading to G2/M cell cycle arrest and apoptosis in cancer cells. |
| SFN + Other Anti-cancer Drugs | Potentiates apoptotic and cytotoxic effects by derepressing Nrf2 pathways and upregulating anti-oxidative responses. |
| SFN + AZ | Enhances efficacy by reducing Nrf2-mediated drug resistance and inhibiting clonogenic growth. |
| CAI (e.g., Acetazolamide) + SFN | Inhibits hypoxia-related pathways involving CAIX, enhancing cancer cell susceptibility and reducing tumor invasiveness. |
| HDAC Inhibitors (e.g., MS-275) + AZ | Targets epigenetic regulation by inhibiting histone deacetylation, causing increased pro-apoptotic gene expression and reduced cancer cell proliferation. |
| HDACi (e.g., Entinostat) + 5-AZA | Synergistically induce cellular stress and apoptosis, improving overall survival rates in cancer patients. |
| Gefitinib + Bevacizumab | Targets EGFR mutations and VEGF/VEGFR pathways, inhibiting angiogenesis and tumor growth. |
| Figitumumab + Chemotherapeutics | Inhibits IGF-1R, affecting cancer proliferation and apoptosis inhibition. |
| Itraconazole + Chemotherapy | Inhibits endothelial cell proliferation and migration, VEGFR2 and FGFR3 activation, enhancing chemotherapy efficacy. |
| Bevacizumab + Other Agents | Inhibits VEGF-mediated angiogenesis, potentiating the effects of other anti-cancer agents (e.g., curcumin, erlotinib). |
| Nitroglycerin + Vinorelbine | Nitric oxide donor inhibiting angiogenesis and downregulating HIF1alpha, leading to apoptosis and improved chemotherapeutic efficacy. |
| Clarithromycin (CAM) + Bortezomib | Enhances endoplasmic reticulum stress-mediated apoptosis, increasing cytotoxic effects in combination with proteasome inhibition. |
| HDACi (e.g., SAHA) + Bortezomib + CAM | Synergistically inhibit cancer cell adaptation to cellular stress, inducing apoptosis. |
| Conatumumab + FOLFIRI | Monoclonal antibody agonist against TRAIL, inducing apoptosis through death receptor signaling, in combination with conventional chemotherapy inhibiting cancer progression. |
Our Services
Alfa Cytology provides a full spectrum of preclinical services to support the development of combination therapies for pancreatic cancer. Our team of experts collaborates closely with clients to design, execute, and optimize combination therapy studies that align with their research goals. Our services include:
Combination Screening and Optimization
We offer high-throughput screening and in-depth analysis of various therapeutic combinations to identify synergistic effects and optimize dosing regimens. Our team utilizes advanced in vitro models, including 2D and 3D cultures of pancreatic cancer cells, to evaluate the efficacy of different drug combinations.
In Vivo Drug Combination Studies
In vivo studies test drug combinations in animal models to evaluate real-world effects like tumor inhibition or survival rates. These tests are crucial in assessing the combination's efficacy and safety before clinical trials.
Data Analysis and Combination Index Calculation
Data from experiments are analyzed using mathematical models to calculate the combination index (CI) or fractional inhibitory concentration (FIC). These values help determine whether the drug combination is synergistic, additive, or antagonistic.
In Vitro Drug Combination Effect Evaluation
This service uses various assays, such as cell viability and apoptosis detection, to measure the biological effects of drug combinations in laboratory settings. It helps determine whether the combined drugs enhance, neutralize, or inhibit each other's effects.
Pharmacokinetic and Toxicology Studies
To ensure the safety and effectiveness of combination therapies, we perform pharmacokinetic (PK) and toxicology studies. These studies help determine the optimal dosing schedule and identify any potential adverse effects associated with the combination therapy.
Why Choose Us?
Tailored Solutions
Advanced Technology
Professional Expertise
Collaborative Approach
At Alfa Cytology, we understand the complexities and challenges of developing effective combination therapies for pancreatic cancer. Our team of seasoned scientists, cutting-edge technologies, and comprehensive preclinical services make us an ideal partner for your research and development needs. We are dedicated to helping you achieve your therapeutic goals by providing expert guidance, innovative solutions, and reliable results. Contact us today to learn more about our services and how we can collaborate on your next project.
Reference
- Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017 Jun 6;8(23):38022-38043. doi: 10.18632/oncotarget.16723. PMID: 28410237; PMCID: PMC5514969.
