Repurposed Cardiovascular Drugs in Pancreatic Cancer Treatment Trials

Introduction to Drug Repurposing in Pancreatic Cancer

Concept of Drug Repurposing

Drug repurposing involves using existing medications, originally approved for other diseases, to treat pancreatic cancer. This strategy capitalizes on established safety profiles and pharmacology, enabling faster clinical translation compared to developing new drugs from scratch. Examples extend from anti-inflammatory agents to cardiovascular and anti-infective drugs, with multiple candidates currently evaluated in preclinical and clinical pancreatic cancer studies.

Rationale for Repurposing Cardiovascular Drugs

Cardiovascular drugs such as beta-blockers, statins, ACE inhibitors, and cardiac glycosides have mechanisms that may interfere with cancer cell growth and microenvironment. For instance, beta-blockers suppress tumor angiogenesis, invasion, and metastasis by blocking beta-adrenergic receptors involved in stress-mediated tumor progression. Statins target cholesterol synthesis pathways, impeding tumor proliferation through disruption of protein prenylation. Cardiac glycosides like digitoxin and digoxin induce apoptosis by affecting ion transport and signaling. These diverse mechanisms justify exploring cardiovascular medications as adjuvants or direct treatments for pancreatic cancer.

Significance of Innovation in Pancreatic Cancer Treatment

Pancreatic cancer remains highly lethal, with a five-year survival rate under 5%. Late diagnosis and resistance to conventional therapies present major challenges. Innovations including drug repurposing offer hope for expanding therapeutic options. By targeting multiple tumor pathways and modifying the tumor microenvironment, repurposed drugs have the potential to improve outcomes. Ongoing clinical trials, especially in the United States, highlight the commitment to integrating repurposed cardiovascular agents into pancreatic cancer treatment paradigms.

Standard Therapeutic Approaches for Pancreatic Cancer

What types of standard therapies are typically used in pancreatic cancer treatment?

Pancreatic cancer treatment usually involves a combination of surgery, chemotherapy, and radiation therapy, tailored to the stage and resectability of the tumor.

Surgery methods such as the Whipple procedure

For localized pancreatic tumors, surgery offers the best chance for cure. The most common surgical approach is the Whipple procedure (pancreaticoduodenectomy), which removes the head of the pancreas along with parts of the stomach, duodenum, gallbladder, and bile duct. Institutions like Johns Hopkins in the United States are prominent centers performing this complex surgery. Advances in imaging and genetic testing have expanded criteria, enabling more patients to qualify for surgical resection.

Chemotherapy regimens like FOLFIRINOX and Gemcitabine

Chemotherapy is fundamental in managing pancreatic cancer, either as adjuvant therapy after surgery or for unresectable and metastatic disease. Two primary regimens are:

• FOLFIRINOX: A combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin. Studies demonstrate it improves median survival to over 11 months compared to gemcitabine, with increased progression-free survival and response rates. However, toxicity is higher, so patient selection (good performance status) is crucial.

• Gemcitabine-based therapy: Gemcitabine alone or combined with nab-paclitaxel remains a standard, especially for patients unable to tolerate FOLFIRINOX. Combination regimens have shown improved survival and response, with manageable side effects (nab-paclitaxel plus gemcitabine survival benefit).

Role of radiation therapy and emerging targeted treatments

Radiation therapy is used mainly for local control or palliative care. While historically limited, advancements in radiation techniques are improving outcomes.

Targeted therapies and immunotherapies are evolving rapidly, with clinical trials testing agents such as PARP inhibitors for BRCA-mutated tumors (EA2192 / APOLLO trial), vaccines, and oncolytic viruses. Genetic profiling is guiding personalized treatment plans, aiming to improve responses where traditional therapies fall short (Mayo Clinic Pancreatic Cancer Studies).

Overall, these standard therapeutics form the cornerstone of pancreatic cancer care, with ongoing research focused on enhancing efficacy and tolerability (Recent advances in pancreatic cancer research).

Therapy Type	Description	Clinical Notes
Surgery	Whipple procedure and distal pancreatectomy	Best for localized tumors; high surgical expertise required (Johns Hopkins Clinical Trials for Pancreatic Cancer)
Chemotherapy	FOLFIRINOX, Gemcitabine (+ nab-paclitaxel)	FOLFIRINOX for fit patients; gemcitabine regimens for broader use (FOLFIRINOX therapy for metastatic pancreatic cancer)
Radiation Therapy	Local control, palliation	Emerging improved techniques for better outcomes (Potential New Therapies for Pancreatic Cancer
Targeted Therapies	PARP inhibitors, genetic mutation-based drugs	Personalized treatments under active clinical evaluation (PARP inhibitor olaparib
Immunotherapy	Vaccines, immune checkpoint inhibitors	Early stage trials seeking to overcome immunosuppressed microenvironment (Pancreatic Cancer Clinical Trials

Innovative Therapeutic Strategies Complementing Traditional Treatment

What innovative strategies are being combined with standard therapies in pancreatic cancer treatment?

Pancreatic cancer treatment is increasingly incorporating innovative strategies alongside standard therapies to tackle the disease's complexity and improve patient outcomes.

One major advance is the rise of personalized medicine for pancreatic cancer, where therapies are guided by genetic mutation profiles. A predominant mutation in pancreatic cancer is KRAS, present in over 90% of cases. New drugs targeting specific KRAS mutations, such as the G12D subtype involved in nearly half of pancreatic cancers, have shown promise by irreversibly binding mutant proteins and inhibiting tumor growth. However, resistance to KRAS targeting remains a challenge, prompting ongoing research into combination therapies to overcome this obstacle.

Cancer vaccines are another promising approach. These vaccines aim to stimulate the immune system to recognize pancreatic cancer cells earlier, potentially preventing progression or recurrence. Personalized mRNA vaccines for pancreatic cancer, designed from a patient’s own tumor cells, are currently in clinical trials, signaling a shift toward tailored immunotherapies.

Due to pancreatic tumors’ immunosuppressive microenvironment, novel methods to modulate this barrier are critical. Techniques such as boiling histotripsy—a non-invasive, ultrasound-based mechanical ablation—are being explored for their potential to disrupt tumor architecture and enhance immune accessibility.

Additionally, oncolytic viruses are under investigation for their ability to selectively infect and destroy pancreatic cancer cells, helping to prime the immune response in conjunction with other therapies. Trials combining these novel modalities with chemotherapy or immunotherapy aim to improve therapeutic effectiveness.

These innovative strategies complement traditional approaches by focusing on early detection, genetic targeting, and enhancing the immune system’s ability to fight pancreatic cancer, striving to overcome the historically poor prognosis associated with this aggressive disease.

Repurposing Cardiovascular Drugs: Mechanisms and Preclinical Evidence

Cardiovascular drugs evaluated for anticancer effects

Several cardiovascular medications have been studied for their potential anticancer properties, particularly in pancreatic cancer models. These include aspirin, beta-blockers, angiotensin receptor blockers (ARBs), statins, and cardiac glycosides like digitoxin. Their widespread clinical use and well-known safety profiles provide a foundation for drug repurposing strategies in pancreatic cancer aimed at improving cancer outcomes.

Mechanisms of action of aspirin, beta-blockers, ARBs, statins

• Aspirin functions by inhibiting cyclooxygenase enzymes COX-1 and COX-2, reducing thromboxane A2 and prostaglandin E2. This leads to decreased platelet aggregation and tumor-promoting inflammation.
• Beta-blockers block beta-adrenoreceptors, impairing catecholamine-induced tumor growth, angiogenesis, invasion, and metastasis.
• ARBs interfere with the renin-angiotensin system by blocking angiotensin II receptors, downregulating VEGF expression and reducing stromal fibrosis.
• Statins inhibit HMG-CoA reductase, lowering cholesterol and inhibiting prenylation of proteins critical for cancer cell proliferation.

These mechanisms have been extensively reviewed in mechanisms and clinical validation of cardiovascular drugs in oncology.

Preclinical studies showing effects on tumor growth, metastasis, and microenvironment

Preclinical models demonstrate that these drugs can modulate the tumor microenvironment and suppress cancer progression. For instance, beta-blockers reduce pancreatic nerve density and tumor proliferation, while ARBs like losartan reduce stromal fibrosis and improve chemotherapy delivery. Statins have shown antiproliferative effects by targeting oncogenic pathways. Aspirin use is associated with prevention of metastasis by inhibiting platelet-tumor cell interactions.

More detailed evidence is available in the cardiovascular and anti-inflammatory drugs in cancer treatment and cardiovascular drugs and anti-cancer effects analyses.

Specific example: digitoxin and cardiac glycosides in pancreatic cancer models

Digitoxin, a cardiac glycoside traditionally used for heart conditions, has been repurposed in pancreatic cancer research. Laboratory studies reveal that digitoxin disrupts cancer cell metabolism, disturbs calcium balance, and induces apoptosis. Clinical trials in the United States are investigating optimal dosing, safety, and patient-specific biomarkers. Cardiac glycosides also exhibit anti-tumor activity by altering membrane potentials and signaling pathways, making them promising candidates for pancreatic cancer treatment.

Further information on digitoxin's anticancer potential and ongoing clinical trials can be found in oncological use of digitoxin.

Clinical Trials Investigating Cardiovascular Agents in Pancreatic Cancer

Overview of clinical trials involving repurposed cardiovascular drugs

Several Cardiovascular drugs and anti-cancer effects are currently being tested in clinical trials as potential treatments for pancreatic cancer. These repurposed agents include Digitoxin pancreatic cancer treatment, Propranolol tumor suppression, and Losartan in pancreatic cancer stroma, all of which have shown promising preclinical activity. Digoxin, a Cardiac glycosides antiproliferative effects, interrupts tumor cell metabolism and triggers apoptosis, while propranolol, a Beta-blockers in tumor progression, may reduce tumor proliferation and nerve density in pancreatic tumors. Losartan, an angiotensin II receptor blocker (ARB), is investigated for its ability to reduce stromal fibrosis and improve drug delivery.

Phase I and II studies with digoxin, propranolol, losartan

The clinical development of digoxin for pancreatic cancer includes trials aiming to identify optimal dosing, safety, and relevant Biomarkers for personalized cancer therapy to personalize treatment. Propranolol is being evaluated for perioperative and advanced disease settings to assess improvements in survival and disease progression. Losartan is part of combination therapies with chemotherapy or experimental agents, with phase 2 trials assessing its efficacy in preventing resistance and enhancing chemotherapy effects.

Limitations of randomized trials showing mixed or negative outcomes

Despite extensive observational and preclinical data supporting Cardiovascular drugs in metastatic and first-line cancer therapy, most randomized clinical trials conducted between 2000 and 2023 failed to demonstrate significant improvements in overall survival or progression-free survival in cancer patients. Many trials involved metastatic cancers and tested these drugs as first-line therapies, often showing no benefit or even potential harm. This discrepancy highlights the limited translation of preclinical promises into clinical benefits.

Importance of rigorous clinical evaluation and biomarkers

Given the mixed outcomes, rigorous clinical trials with well-defined endpoints and the integration of validated biomarkers are critical. Biomarkers for personalized cancer therapy can identify patients most likely to benefit from repurposed cardiovascular drugs by elucidating mechanisms of action and resistance. Personalized medicine approaches combined with robust trial designs will determine the true value of these agents in pancreatic cancer management.

Digitoxin: A 250-Year-Old Heart Drug with New Potential

What is the history and traditional use of digitoxin?

Digitoxin is a cardiac glycoside derived from the foxglove plant (Digitalis purpurea heart medicine) and has been prescribed since the 18th century (18th century heart medicine. Traditionally, it has been used to treat heart conditions such as arrhythmias and heart failure by regulating heart rhythm and strengthening cardiac contractions.

What laboratory evidence supports digitoxin’s effects on pancreatic cancer cells?

Recent laboratory studies have revealed that digitoxin disrupts cancer metabolism, interferes with calcium balance within cells, and can induce cancer cell death or halt cancer cell division. These effects have been observed across five pancreatic cancer cell lines, suggesting broad anti-tumor potential.

What are the goals of the ongoing clinical trial involving digitoxin?

A clinical trial led by researchers at the University of Skövde cancer research in Sweden aims to explore digitoxin’s safety profile, optimal dosage, and the relevance of specific biomarkers for personalized cancer therapy in humans. The study involves pancreatic cancer patients and uses five different cell lines to assess varied responses, facilitating personalized treatment strategies.

How does the personalized approach using varied cancer cell lines benefit the research?

Since pancreatic cancer is highly heterogeneous, using multiple cell lines enables the identification of differential drug sensitivities and the discovery of personalized treatment biomarkers. This approach can help tailor treatments to individual patient profiles, increasing the chances of clinical success.

What are the challenges and prospects for digitoxin as a pancreatic cancer therapy?

Pancreatic cancer is aggressive with less than 5% five-year survival (Pancreatic cancer survival rates. While digitoxin shows promise in vitro and in preclinical studies, challenges include determining safe and effective drug levels for cancer treatment, managing potential toxicity, and validating clinical efficacy. If successful, digitoxin could offer an additional therapeutic option where current treatments are limited.

Mechanisms Underpinning Beta-Blockers and ARBs in Pancreatic Cancer Therapy

How do beta-blockers inhibit angiogenesis and tumor invasion?

Beta-blockers block beta-adrenoreceptors, which mediate the effects of stress hormones such as catecholamines. By doing so, they inhibit several cancer-promoting processes including tumor angiogenesis, invasion, and metastasis. Experimental studies have shown that these drugs reduce proliferation and spread of various cancer cells, including pancreatic cancer, through suppression of pathways that are normally activated by adrenergic signaling (Beta-blockers in tumor progression).

What is the impact of propranolol on pancreatic nerve density and patient survival?

Propranolol, a non-selective beta-blocker, has demonstrated the ability to lower pancreatic nerve density, which is typically elevated in pancreatic cancer and can promote tumor growth. Studies in pancreatic cancer models revealed that propranolol reduces tumor proliferation and invasiveness. Clinical investigations further suggest improved survival outcomes in patients treated with propranolol, highlighting its potential as a supportive therapy in pancreatic cancer management (Propranolol impact on pancreatic cancer progression).

How does losartan affect stromal fibrosis, TGF-β signaling, and drug delivery in pancreatic cancer?

Losartan, an angiotensin receptor blocker (ARB), targets the angiotensin II type 1 receptor (AT1R) to inhibit TGF-β function. This results in decreased stromal fibrosis—a dense layer of connective tissue surrounding pancreatic tumors that limits drug penetration. By reducing fibrosis, losartan improves drug delivery and enhances immune responses in preclinical pancreatic cancer models. These effects suggest losartan could help overcome the treatment resistance mediated by the tumor microenvironment (Losartan in pancreatic cancer stroma.

What combination trials in the US involve losartan and chemotherapy for pancreatic cancer?

In the United States, phase II clinical trials are exploring the combination of losartan with chemotherapy regimens such as FOLFIRINOX. Losartan is being tested alongside experimental drugs like 9-ING-41 (Elraglusib), which inhibits GSK-3β—a kinase involved in chemotherapy resistance. The trial’s goal is to assess whether adding losartan can suppress tumor progression and improve progression-free survival by modulating the tumor stroma and overcoming chemoresistance (Combination therapy for metastatic pancreatic adenocarcinoma).

These cardiovascular drugs, through modulation of tumor biology and microenvironmental factors, represent promising adjuncts to pancreatic cancer therapy under investigation in clinical settings (Cardiovascular drugs and anti-cancer effects).

Challenges and Limitations in Translating Cardiovascular Drugs to Oncology

What accounts for the discrepancy between promising preclinical data and clinical trial outcomes?

Cardiovascular drugs like aspirin and cancer risk reduction, statins and cancer risk, and metformin mitochondrial impact have shown significant anti-cancer effects in preclinical models. For instance, aspirin inhibits COX enzymes reducing tumor growth factors, statins affect cholesterol and protein prenylation pathways, and metformin modulates cellular metabolism and insulin signaling. However, these encouraging laboratory and observational findings have not translated into significant survival benefits in randomized clinical trials. The complex tumor biology, differences in drug metabolism in human subjects, and the advanced cancer stage in enrolled patients may contribute to this gap.

Why do many randomized trials show a lack of significant survival benefits?

A systematic review of 67 randomized clinical trials showed that most cardiovascular drugs in metastatic and first-line cancer therapy did not improve overall or progression-free survival in cancer patients. Only a small fraction of studies with limited patient numbers reported any survival advantage. Many trials tested these medications in metastatic settings or as first-line therapies where aggressive disease may overshadow moderate drug effects. Some studies even observed worse outcomes.

What are potential reasons for inconclusive or negative trial results?

Factors include heterogeneity in patient populations, late-stage disease settings, insufficient dosing or exposure, and interactions with standard cancer therapies. Additionally, cardiovascular drugs may not effectively penetrate tumor microenvironments or may lack potency as monotherapies. The lack of biomarker-driven patient selection could dilute potential benefits.

Why is exploring cardiovascular drugs for cancer prevention considered more promising?

Emerging evidence suggests these drugs might be more effective in high-risk or healthy populations by preventing cancer initiation or progression rather than treating established tumors. This preventive approach requires different trial designs focused on long-term outcomes and cancer incidence rather than immediate survival, which could better harness these drugs' properties.

How do these challenges impact trial design and patient selection?

Future clinical trials should prioritize earlier disease stages, incorporate molecular and genetic biomarkers for patient stratification, and employ combination therapies to enhance efficacy. Selecting appropriate endpoints and doses tailored to cancer biology is crucial. Understanding pharmacodynamics and resistance mechanisms will inform targeting strategies, improving translational success.

This nuanced understanding underscores the complexities of mechanisms and clinical validation of cardiovascular drugs in oncology and the importance of well-designed clinical trials to establish true clinical benefits.

Integrating Repurposed Drugs Within Multidisciplinary Pancreatic Cancer Care at Hirschfeld Oncology

How does the multidisciplinary team at Hirschfeld Oncology collaborate to improve patient outcomes in pancreatic cancer?

At Hirschfeld Oncology, the management of pancreatic cancer is a coordinated effort among a comprehensive multidisciplinary team comprised of specialized oncologists, surgeons, nurses, and supportive care staff. This team works closely to develop personalized treatment plans that integrate both standard therapies and repurposed drugs, optimizing patient outcomes.

The collaboration begins with accurate early diagnosis and genetic profiling to guide therapy selection. Surgeons assess resectability and advise on surgical options, while oncologists recommend systemic therapies tailored to the patient's cancer subtype and condition. Nurses and support staff ensure symptom management, treatment compliance, and psychosocial support.

Importantly, Hirschfeld Oncology actively incorporates clinical trial opportunities into patient care. Trials offering access to innovative therapeutics like PARP inhibitors for BRCA-mutated pancreatic cancer are combined with repurposed cardiovascular agents such as beta-blockers and ARBs, which research suggests may improve cancer control by modulating tumor microenvironment and fibrosis.

This integrative approach leverages evidence-based medicine and emerging drug repurposing strategies in pancreatic cancer to combat the aggressive nature of pancreatic cancer. Through tight coordination, the multidisciplinary team elevates survival chances and maintains quality of life by delivering personalized, comprehensive care that addresses both tumor biology and patient well-being.

Compassionate Care and Experienced Leadership in Pancreatic Cancer Management

How does Hirschfeld Oncology integrate compassion and experience in its pancreatic cancer treatment plans?

Hirschfeld Oncology combines deep medical expertise with a strong commitment to compassionate care in treating pancreatic cancer. The center focuses on providing patient-centered treatment plans that are tailored to each individual's unique condition and needs. By integrating the latest scientific advances with a personalized approach, Hirschfeld Oncology ensures that patients receive care that not only targets the disease but also supports their emotional and psychological well-being.

This approach involves clear, empathetic communication and multidisciplinary collaboration, which helps patients and families navigate the complex treatment journey. The team prioritizes addressing both the physical symptoms of pancreatic cancer and its emotional impacts, fostering trust and hope throughout the process.

What role does Dr. Azriel Hirschfeld play in the pancreatic cancer treatment team?

Dr. Azriel Hirschfeld leads the pancreatic cancer treatment team with a strong emphasis on innovation and patient quality of life. He is instrumental in integrating advanced treatment strategies such as metronomic chemotherapy, which involves low-dose, frequent administration to maximize tumor control while minimizing toxic side effects.

His leadership ensures that treatment plans at Hirschfeld Oncology are evidence-based but also considerate of the patient's overall experience. Dr. Hirschfeld advocates for combining scientific progress with compassionate care, working closely with other specialists to develop therapies that improve survival and maintain well-being. This balance makes Hirschfeld Oncology a trusted center for managing this challenging disease.

Future Directions: Combining Cardiovascular Agents with Emerging Pancreatic Cancer Therapies

How might cardiovascular drugs synergize with immunotherapy, targeted agents, and chemotherapy in pancreatic cancer?

Cardiovascular drugs, such as beta-blockers, aspirin, and ARBs like losartan, have shown promising effects in preclinical pancreatic cancer studies by modulating tumor growth, angiogenesis, and stromal interactions. Emerging research suggests combining these repurposed agents with immunotherapies and chemotherapy could enhance treatment efficacy. For example, losartan’s ability to reduce stromal fibrosis improves drug delivery and immune infiltration, potentially amplifying immunotherapy and chemotherapy responses.

What efforts exist to overcome the pancreatic tumor microenvironment barriers?

The dense and immunosuppressive tumor microenvironment in pancreatic cancer remains a major obstacle to effective treatment. Researchers are investigating strategies to modify this microenvironment, including the use of ARBs like losartan to reduce fibrosis and improve perfusion. Additionally, clinical trials are exploring combinations of chemotherapy with immune-modulating agents, aiming to unlock immunosuppression and boost immune cell access to tumors.

Which novel molecular targets are promising for the future?

Significant advances in targeting pancreatic cancer genetics include the recent development of drugs aimed at the KRAS G12D mutation, present in nearly half of pancreatic cancers. This mutation has historically been ‘undruggable,’ but new molecules irreversibly modifying KRAS G12D show potential in preclinical models for halting tumor growth. Another promising area is the tumor suppressor protein PI3K-C2Y, whose role in limiting tumor cell proliferation may provide novel therapeutic angles.

How is US-based clinical research expanding therapeutic options?

United States research institutions and clinical trial networks are at the forefront of evaluating integrated therapies combining repurposed cardiovascular drugs with immunotherapy and targeted agents. Trials such as those involving losartan and novel KRAS inhibitors exemplify efforts to translate promising laboratory findings into patient benefits. Additionally, initiatives like the NCI-supported studies and Mayo Clinic’s multifaceted trials emphasize personalized medicine by combining genetic profiling, biomarker discovery, and innovative treatments to broaden pancreatic cancer therapeutic strategies.

This multi-pronged future direction underscores the importance of collaborative approaches that integrate drug repurposing strategies in pancreatic cancer, molecular targeting, and immune modulation to improve outcomes for pancreatic cancer patients.

Conclusion: The Promise and Challenges of Cardiovascular Drug Repurposing in Pancreatic Cancer

The Potential Benefits of Repurposed Cardiovascular Drugs

Cardiovascular drugs such as aspirin, beta-blockers, and statins have demonstrated promising anti-cancer activities in preclinical and observational studies. These drugs may inhibit tumor growth, angiogenesis, metastasis, and modulate immune responses, offering potentially affordable and accessible adjunct therapies for pancreatic cancer. Notably, aspirin reduces pro-inflammatory mediators, beta-blockers suppress tumor invasion, and statins interfere with cholesterol-related pathways important for tumor cell survival. Early evidence suggests these agents might enhance treatment efficacy or improve survival in patients, especially when combined with chemotherapy or targeted treatments.

Limitations of Current Clinical Trials

Despite encouraging laboratory findings, large randomized clinical trials have so far failed to consistently demonstrate significant survival benefits for pancreatic cancer patients using these repurposed cardiovascular drugs. Many studies were conducted in late-stage disease settings and had heterogeneous patient populations. Moreover, some clinical trials even showed potential harm or no improvement in progression-free survival. These limitations highlight the complexity of translating preclinical observations into effective clinical therapies.

The Role of Multidisciplinary Teams and Compassionate Care

Given the aggressive nature of pancreatic cancer and limited approved therapies, a multidisciplinary care approach remains critical. Teams integrating oncologists, surgeons, radiologists, pharmacists, and supportive care specialists ensure personalized management and optimal use of existing and experimental treatments. Compassionate care and patient education about investigational therapies and clinical trial options are essential to navigate uncertainties and maintain quality of life.

Importance of Continued Research and Clinical Trials

To unlock the full potential of cardiovascular drug repurposing in pancreatic cancer, ongoing research is vital. Well-designed, sufficiently powered clinical trials targeting early-stage disease and tailored patient subgroups may better clarify efficacy. Additionally, understanding the molecular mechanisms and identifying biomarkers predictive of response can refine treatment approaches. Integration of multidisciplinary expertise and collaboration in clinical research will be key to developing effective, safe, and personalized therapies for this devastating disease.