DECODING CANCER: HOW TARGETED PROTEOMICS IS SHAPING ONCOLOGY

Targeted proteomics is a powerful approach that enables researchers to analyze specific proteins within complex biological systems, offering crucial insights into cancer metabolism and therapeutic targets. As technological advancements push the field forward, Dr. Petrović explores both the opportunities and challenges of integrating proteomics into oncology research and clinical practice.

In this interview, Oncology Compass Digest discusses with Dr. Petrović the potential of targeted proteomics in advancing cancer treatment, the hurdles in methodology and real-world application, and the evolving role of liquid biopsies and AI in the field.

I come from a biochemical background, and I completed my PhD at the University of Belgrade. My early work focused on developing tumor drugs based on gold complexes. Later, during my postdoc at NTNU in Trondheim, Norway, I specialized in targeted proteomics and the role of signaling molecules in cancer.

I consider myself a protein chemist, meaning my research has been deeply focused on proteins — their structure and how they impact cancer metabolism. My training emphasized protein purification and isolation, so for me, sample preparation is key to obtaining reliable results downstream.

When we talk about targeted proteomics, we are considering mass spectrometry-based approach that focuses on a specific subset of proteins that belong to a similar group, either based on their structure, function, or other properties.

Unlike traditional discovery proteomics, which aims to identify as many proteins as possible, targeted proteomics selectively analyzes a predefined set of proteins within a biological sample and focuses on detecting and quantifying specific proteins of interest with high accuracy and reproducibility.

For example, I was working with signaling kinases, a class of enzymes that introduce phosphate groups onto other proteins to regulate their function.

Targeted proteomics is particularly valuable in oncology, where we study such key proteins involved in cancer metabolism, signaling pathways, and drug responses for biomarker validation, disease monitoring, and personalized medicine development.

The main driver of current proteomics research in cancer is mapping out in detail the signaling pathways and metabolism of cancers. The hope is that if we fully understand these mechanisms, we will be able to precisely target critical steps in their metabolism that lead to progression, metastasis, or drug resistance.

Ideally, we could use targeted proteomics to characterize tumors down to the last protein and use that knowledge to enable the development of new therapies or improve how existing treatments are applied.

While we have a solid understanding of how to analyze proteomics data, the biggest challenges lie in the methodology and technical aspects of sample preparation. Modern mass spectrometry techniques and solutions generate incredibly high-quality data — so high, in fact, that they reveal inconsistencies in how samples are prepared. Lack of standardization in sample preparation introduces bias and makes comparing results across different studies quite challenging.

The complexity of the starting material is another major hurdle, compounded by biological diversity across individuals, tissues, and even within the same patient over time.

Addressing these challenges is crucial before we can make reliable interpretations relevant to potential clinical applications.

The biggest barrier is logistics. Maintaining and running a proteomics facility requires significant resources — expensive instruments, costly instrument time, and substantial IT infrastructure to handle and interpret results.

Unlike routine lab work, proteomics analysis demands high computing power and considerable time. The main bottleneck is actually the production of data.

Even if we perfected and standardized sample preparation methods today, we would still need major infrastructure investments to streamline sample analysis and integrate results into clinical decision-making.

Liquid biopsies are incredibly promising because they are relatively noninvasive and easy to obtain and preserve. This is crucial for patient comfort, confidence, compliance, and sampling practicality in clinical settings.

The most common liquid biopsy is a simple blood sample, which can provide valuable insights into a patient’s physiology. But other bodily fluids — especially those from hard-to-reach areas — could offer even deeper insights.

For example, cerebrospinal fluid could help us understand neurological conditions, while fluid from specific tumor microenvironments might reveal localized metabolic changes. If we develop smart methods to process these samples and extract meaningful data, liquid biopsies could revolutionize how we monitor and treat cancer.

Single-cell proteomics is extremely important in building our understanding of how tumors function and how the life cycles of different cell populations within a tumor evolve over time. This knowledge could help us develop therapies that target tumors at specific stages of their life cycle, which is crucial for curbing the progression of the disease.

However, when it comes to personalized medicine, we still have a long way to go before single-cell proteomics becomes a routine diagnostic, decision-making, or treatment tool. That said, in certain cases — such as blood cancers or highly diffuse tumors — single-cell proteomics could offer major benefits. At this stage of current research, we need to see more large-scale applications before they become widely adopted in clinical settings.

Before we can develop personalized cancer vaccines, we need to gather extensive data and refine our models. The first step is improving diagnostics — identifying the specific proteins and molecular markers unique to different cancers. Once we achieve that, we’re already halfway to creating better treatments.

So, while the potential is there, we still have foundational work to do before targeted proteomics can fully support personalized cancer vaccines.

Proteomics has the potential to greatly improve our understanding of biomarkers. Instead of thinking of biomarkers in the traditional sense as single molecules detected in the body, proteomics allows us to identify changes at a much finer level — such as post-translational modifications or phosphorylation patterns on proteins. Here, we are considering parts of the molecule, specific parts of a protein being modified in different ways — having different structures or different sequences as constituting a biomarker. These molecular changes could serve as highly specific biomarkers, improving patient stratification for precision treatments.

AI is a fascinating development, and it’s hard not to be optimistic about its potential. Given the vast complexity of proteomics data, AI and machine learning could help us solve several difficult tasks and manage and interpret the data more efficiently. We haven’t yet seen widespread AI adoption in mass spectrometry and proteomics, but if there’s any field in life sciences that stands to benefit, it’s this one. The sheer volume and complexity of proteomics and multiomics data make AI an ideal tool for extracting meaningful insights from biological samples. I’m hopeful that future developments in AI will help us tackle some of the toughest challenges in this field.

The communication skills of oncologists, particularly their ability to convey competence, honesty, and empathy, significantly influence patient trust and treatment adherence. Research indicates that enhanced expression of these qualities by oncologists led to increased patient trust, improved expectations of treatment success, and a higher likelihood of patients recommending their oncologists.¹

Furthermore, patient-centered communication has been associated with greater patient satisfaction and lower emotional distress, which are essential for informed decision-making and adherence to treatment plans.^2,3

Conversely, a lack of effective communication can lead to misunderstandings, decreased trust, and reduced adherence to prescribed therapies, ultimately compromising patient outcomes.

Established in 2018, yeswecan!cer was born out of a critical need: to provide cancer patients with an accessible, stigma-free environment where they could share their experiences, seek advice, and find support.⁴

Hoppe recognized that while medical advancements were extending lives, many patients still faced a crushing sense of isolation. By leveraging digital technology, yeswecan!cer created a space where no patient has to navigate their journey alone.⁴

At the heart of the initiative is the YES!APP, a free, secure, and anonymous digital platform that connects cancer patients, survivors, and supporters. The app serves as a virtual meeting place where users can engage in peer-to-peer discussions, access expert advice, and build a support network tailored to their unique needs. With features designed to encourage open dialogue and emotional support, the YES!APP helps patients regain control of their lives beyond their diagnosis.⁴

Users of the YES!APP can participate in topic-specific chat groups, offering a space for discussions on various aspects of the cancer journey, from treatment options and side effects to emotional challenges and coping strategies. The app also includes one-on-one messaging features, allowing patients to privately connect with those who share similar experiences. This fosters an environment where individuals can share advice, encouragement, and personal insights in a safe and supportive setting.⁴

Beyond peer-to-peer support, yeswecan!cer facilitates interactions between patients and medical professionals. Through live Q&A sessions, webinars, and expert discussions, patients can gain valuable insights from oncologists, psychologists, and other healthcare professionals. These sessions cover a range of critical topics, including the latest advancements in cancer treatment, nutrition, and mental well-being. This direct access to specialists helps patients make more informed decisions about their health while reinforcing the importance of holistic care.⁴

The YES!APP also features a mentoring program, where experienced cancer survivors can guide newly diagnosed patients through their treatment journeys. This mentorship initiative fosters a strong sense of community and reassurance, helping individuals navigate the overwhelming aspects of their diagnosis with the support of those who have been through similar experiences. Additionally, the app integrates a resource library, providing users with educational materials, recommended readings, and curated content from reputable cancer organizations.⁴

In addition to the YES!APP, yeswecan!cer has made waves with its YES!CON event, Germany’s first and largest cancer convention. Launched in 2020, YES!CON brings together medical experts, patients, caregivers, and advocates to discuss the future of cancer care.

This annual event creates an open forum where patients are not just passive recipients of care but active participants in shaping their own treatment journeys. Through panel discussions, expert-led workshops, and patient testimonials, YES!CON fosters a dynamic conversation around cancer, empowering individuals with knowledge, resources, and hope.⁴

The success of yeswecan!cer is reflected in the voices of those it serves. Take, for instance, the story of Anna, a 38-year-old breast cancer survivor. Before discovering the YES!APP, Anna felt disconnected from her peers and overwhelmed by her diagnosis. Traditional support groups didn’t fit her needs, and online forums lacked the security she desired. Through yeswecan!cer, she found a community that understood her struggles, helped her navigate treatment decisions, and provided emotional reassurance.⁴

Anna’s experience is not unique. Thousands of cancer patients have turned to yeswecan!cer as a vital resource, underscoring the need for digital tools in oncology care. Beyond patient-to-patient support, the platform also facilitates discussions between patients and healthcare professionals, fostering a more holistic approach to treatment and recovery.

While platforms like yeswecan!cer have made significant strides, their full potential can only be realized through collaboration. Oncologists play a crucial role in guiding patients toward these resources, ensuring they receive not only medical care but also psychological and emotional support. By integrating digital patient communities into standard oncology practice, healthcare professionals can enhance patient engagement, treatment adherence, and overall well-being. Pharmaceutical companies also have an opportunity to contribute. Investing in digital health initiatives like yeswecan!cer not only demonstrates a commitment to patient-centric care but also facilitates real-world data collection, which can inform better treatment strategies. Through partnerships and sponsorships, pharma companies can help expand these platforms, making them even more accessible to diverse patient populations.

The future of cancer care is not just about better treatments but also about better communication. yeswecan!cer is leading the way, but its success depends on a collective effort. Oncologists, healthcare providers, and industry leaders must recognize the power of digital patient communities and actively support their growth. By embracing platforms like yeswecan!cer, we can ensure that no patient faces cancer alone.

A cancer diagnosis is not just a medical event — it is a life-altering crisis. Beyond the physical and emotional toll, patients are thrown into a healthcare system that is fragmented, complex, and often overwhelming. If we truly believe in patient-centered care, structured patient navigation should no longer be an afterthought but a fundamental pillar of oncology treatment.

Every year, approximately 500,000 people in Germany are diagnosed with cancer.¹ For many, the moment of diagnosis is followed by a flood of unanswered questions: Which specialist should I see? What treatments are available? How do I deal with the paperwork?

Who will help me with financial and psychological challenges? Patients and their families must navigate a maze of referrals, hospital visits, insurance claims, and rehabilitation options — often with little or no guidance.

Healthcare professionals do their best, but the system itself is not designed to prioritize patient navigation. With oncologists, radiologists, surgeons, palliative care specialists, and general practitioners all involved in treatment, the lack of structured coordination leads to delays, distress, and in some cases, worse clinical outcomes.²

This is where patient navigation programs have been proven to make a difference. Studies have shown that structured navigation improves treatment adherence, reduces stress, and enhances overall satisfaction with care.

It is particularly critical for patients from disadvantaged backgrounds, who may struggle with additional barriers to accessing timely treatment.^3,4

Despite the clear benefits, patient navigation is still not standard practice in many healthcare systems — including Germany’s.

The Onkolotse program, launched by the Saxon Cancer Society (Sächsische Krebsgesellschaft e.V.), is one of Germany’s most promising patient navigation initiatives.

Onkolotsen, or “oncology pilots,” are trained professionals who guide patients and their families through every stage of their cancer journey — from diagnosis and treatment to rehabilitation and palliative care.

Unlike doctors, their role is not to provide medical treatment, but to offer personalized, non-clinical support that ensures patients do not feel lost in the system.⁵

Currently, approximately 340 Onkolotsen operate across Germany, working in hospitals, outpatient clinics, and even independently via online platforms. Patients can access Onkolotsen through medical referrals, health insurance programs, or direct outreach.

However, access remains inconsistent, with insurance coverage varying widely depending on the provider.⁶

This raises an important question: Why isn’t this service universally available to all cancer patients?

The presence of an Onkolotse can make an enormous difference in a patient’s experience. These professionals fulfill multiple critical functions:^5,6

Onkolotsen help coordinate medical appointments, explain treatment plans, and provide financial and social support guidance.

They ensure patients understand their diagnosis and treatment options, helping them make informed decisions.

Cancer is not just a physical illness; it takes a significant emotional toll. Onkolotsen offer coping strategies and connect patients with mental health resources.

By facilitating communication between different healthcare providers, they prevent delays and ensure smoother transitions between treatment phases.

These services have the potential to not only enhance the patient’s well-being but also improve adherence to treatment, reduce hospital readmissions, and contribute to better long-term outcomes.^3,4

And yet, instead of being a guaranteed part of cancer care, the availability of Onkolotsen depends on insurance policies and regional support structures.

Despite overwhelming evidence supporting patient navigation, programs like Onkolotse remain underfunded and underutilized.

The fact that access to an Onkolotse can depend on an individual’s insurance coverage is unacceptable. Cancer does not discriminate, and neither should patient support services.

To ensure every cancer patient benefits from structured navigation, systemic change is needed:

Onkolotsen services should be integrated into Germany’s national oncology care framework.

Health insurance providers should be required to cover navigation services, removing financial barriers for patients.

Increased investment in training programs will ensure that more Onkolotsen can be available across Germany.

Many patients do not even know that Onkolotsen exist. Public campaigns should highlight their availability and importance.

Cancer care must go beyond surgery, chemotherapy, and radiation — it must address the full spectrum of patient needs, including logistical coordination and emotional resilience.

The Onkolotse model is a shining example of how patient navigation can transform cancer care, but its potential will remain limited unless it becomes a fully recognized and funded part of the healthcare system.

Screening plays a vital role in lowering both the incidence and mortality rates of colorectal cancer by detecting the disease in its early stages or identifying precancerous polyps. Studies suggest that widespread participation in screening programs could significantly decrease the risk of death from colorectal cancer. This underscores the urgent need for improved screening strategies and enhanced accessibility to these programs.³

Colonoscopy is considered the gold standard for colorectal cancer screening.⁴ Colonoscopy allows for direct visualization of the colon and rectum, enabling the detection and removal of precancerous polyps during a single examination. It is highly sensitive and has the dual advantage of prevention and diagnostics.⁵

However, the invasive nature of the procedure, the need for extensive bowel preparation, and associated discomfort deter some individuals from undergoing it.⁶ Additionally, the cost and availability of colonoscopy can be significant barriers, especially in resource-limited settings.⁷

Another useful screening method is sigmoidoscopy, which allows visualization of the lower part of the large bowel. However, its effectiveness is limited in detecting certain types of colorectal cancer and is gender specific.⁸

Other commonly used screening methods include stool-based tests, such as the fecal occult blood test (FOBT), including enzymatic and immunochemical techniques. These tests detect traces of blood in stool samples, which can be a colorectal cancer indicator.

While they are patient-friendly, noninvasive, and widely accessible, they require frequent repetition and possess lower sensitivity compared to other methods, especially for detecting advanced disease.⁹

Although these traditional methods play a significant role in early detection, more effective and patient-friendly approaches are needed.

Recent advancements have led to new screening methods designed to be less invasive while improving detection rates. One promising noninvasive option is multi-target stool DNA testing, such as the first at- home stool test approved by the FDA, the Cologuard test.¹⁰ This method analyzes genetic markers associated with colorectal cancer, offering higher sensitivity than standard fecal immunochemical testing.¹¹

However, concerns about its specificity persist, as this can lead to an increased rate of false positives and unnecessary follow-up colonoscopies.¹²

Another innovation in the form of blood-based biomarker tests has been brought to the market. In July 2024, the FDA approved the Shield blood test, designed to detect genomic and epigenomic alterations of cell-free DNA (cfDNA) associated with colorectal cancer.¹³

Shield blood tests show strong sensitivity for detecting colorectal cancer and represent a less invasive option for individuals reluctant to undergo stool-based tests or endoscopic procedures.

However, ongoing research is still focused on improving its accuracy since it has lower sensitivity for detecting precancerous lesions than traditional colonoscopy.¹⁴

Increased integration of AI-assisted colonoscopy systems into routine clinical practice shows promise in standardizing screening outcomes and improving diagnostic accuracy. Several randomized controlled trials demonstrated that AI-based detection systems improve polyp and adenoma detection rates, ultimately enhancing the overall effectiveness of colonoscopy in terms of prevention and diagnostics.¹⁵

The future of colorectal cancer screening involves integrating multiple approaches to maximize early detection while ensuring accessibility and patient comfort. One such example is capsule endoscopy, a technology that involves swallowing a small capsule equipped with a camera to capture images of the gastrointestinal tract.¹⁶

Although not yet widely adopted as a screening tool, capsule endoscopy has been shown to be safe and promising as a noninvasive method for colorectal cancer detection in the Danish CareForColon2015 randomized controlled trial.¹⁷ Current research and innovations in colon capsule endoscopy are focused on integrating artificial intelligence into image analysis to improve the detection, localization, and characterization of findings.¹⁸

Multiple ongoing clinical trials are evaluating the next generation of colorectal cancer screening tools. The effectiveness of highly sensitive and noninvasive screening options, such as liquid biopsies, which detect circulating tumor DNA (ctDNA) in the blood, is currently being investigated as a tool in the screening and clinical management of patients with colorectal cancer.^19,20

Researchers are also exploring personalized screening strategies incorporating genetic markers, microbial biomarkers, and lifestyle risk factors to tailor screening recommendations for individual patients.²¹

Despite various available options, participation rates in screening programs remain low. This is due to several factors, including fear of invasive procedures, lack of awareness, and limited access to healthcare. To address these barriers, initiatives during Colorectal Cancer Awareness Month focus on the importance of early detection.

Organizations such as the World Health Organization and the American Cancer Society lead campaigns that highlight the significance of early detection in fighting colorectal cancer. Hospitals often hold free or subsidized screening events to encourage more people to participate.

Additionally, continuing medical education helps keep physicians informed about the latest screening guidelines and innovations. By implementing these initiatives and exploring innovative approaches, the medical community can significantly reduce the burden of colorectal cancer, as early detection is a key strategy for lowering mortality rates.

The 7-year follow-up of the phase 2 ABC trial assessed the long-term efficacy of ipilimumab plus nivolumab versus nivolumab monotherapy in patients with melanoma brain metastases.

The study, conducted across multiple Australian cancer centers, highlights the sustained benefit of combination immunotherapy and its role in shaping treatment guidelines for this challenging patient population.¹ Among asymptomatic patients with no prior brain-directed therapy, the intracranial response rate was significantly higher in the combination therapy group (n=18; 51%) compared to nivolumab monotherapy (n=5; 20%). These response rates suggest that dual checkpoint inhibition effectively overcomes the immune-evasive mechanisms of melanoma within the central nervous system (CNS).

The durable control of brain metastases with combination therapy is particularly noteworthy, given the historically poor prognosis associated with CNS involvement in melanoma.

Notably, 7-year intracranial progression-free survival was 42% in the combination cohort versus 15% with nivolumab alone, underscoring the long-term disease control provided by ipilimumab plus nivolumab.¹

Overall survival at 7 years was markedly improved with combination therapy (48% vs. 26%), a finding that reinforces the life-prolonging potential of dual checkpoint blockade.

Additionally, the safety profile of the combination remained consistent with previous reports, indicating no unexpected late-onset toxicities. While the benefits of combination therapy are clear, its use must be balanced against the increased risk of immune-related adverse events.

The study also highlights the need for further exploration of stereotactic surgery in this evolving treatment paradigm, as trials investigating the integration of radiotherapy with checkpoint inhibitors are ongoing.¹

The EORTC 1325/KEYNOTE-054 phase III trial explored the prognostic and predictive roles of body mass index (BMI) and type 2 diabetes mellitus (T2DM) in melanoma patients receiving pembrolizumab.²

This study addressed a crucial gap in understanding the interplay between metabolic conditions and immunotherapy efficacy, as obesity and metabolic dysfunction have been implicated in immune modulation.

Results demonstrated a U-shaped relationship between BMI and recurrence-free survival (RFS), with patients at the extremes of BMI (20 or 35 kg/m²) exhibiting worse outcomes compared to those with a BMI of 25 kg/m².

This suggests that both underweight and obese patients may have an altered immune environment that affects tumor surveillance and response to treatment.

Interestingly, BMI was not predictive of pembrolizumab effectiveness, indicating that while it is a prognostic factor for melanoma progression, it does not influence response to immune checkpoint inhibition.²

Additionally, BMI was not associated with an increased risk of immune-related adverse events.

T2DM, on the other hand, was not significantly associated with RFS or pembrolizumab efficacy, suggesting that hyperglycemia and insulin resistance do not markedly impact melanoma progression in this context. However, given the complex relationship between metabolism and immune function, further studies are warranted to assess whether glycemic control or other metabolic interventions could modify immunotherapy outcomes.

The findings from this study reinforce the need for a nuanced understanding of host factors in melanoma treatment and suggest that BMI may serve as a biomarker for disease prognosis rather than treatment response.²

A post hoc analysis of the KEYNOTE-716 trial examined whether primary tumor location influences the efficacy of adjuvant pembrolizumab in patients with resected stage IIB/IIC melanoma.³

Given the biological differences in melanomas arising from different anatomic sites, this analysis provides valuable insights into the consistency of pembrolizumab’s benefit across subgroups.^3,4

The study evaluated recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) across different tumor locations, including the head/ neck, trunk, and extremities. Across all subgroups, pembrolizumab demonstrated a consistent benefit over placebo, reinforcing its role as an effective adjuvant therapy.

The hazard ratios (HRs) for RFS were 0.60 for head/neck tumors, 0.57 for trunk tumors, and 0.69 for extremities, demonstrating a robust protective effect.

Similarly, DMFS HRs favored pembrolizumab across subgroups, with the most pronounced benefit observed in trunk (HR 0.59) and extremity tumors (HR 0.53).³

These findings highlight the broad applicability of adjuvant pembrolizumab and suggest that primary tumor location does not significantly impact treatment benefit.

Given that the tumor microenvironment can differ based on location, 5 these results provide reassurance that pembrolizumab remains an effective intervention regardless of these variations.

Importantly, the study reinforces the importance of adjuvant therapy in stage II melanoma, a population that was historically considered lower risk but has since been recognized as having significant recurrence potential.⁶

The findings further support pembrolizumab as a standard treatment option for patients with resected high-risk melanoma, and future studies may explore whether additional biomarkers can refine patient selection for adjuvant immunotherapy.

These recent melanoma studies highlight key advances in immunotherapy efficacy, prognostic factors, and adjuvant treatment strategies.

The 7-year ABC trial confirms the long-term benefit of ipilimumab plus nivolumab for brain metastases, while the KEYNOTE-054 analysis emphasizes the prognostic role of BMI without affecting pembrolizumab efficacy.

Meanwhile, the KEYNOTE-716 post hoc analysis demonstrates pembrolizumab’s consistent benefit across different primary tumor locations, reinforcing its role as an essential component of melanoma treatment.

Together, these findings contribute to a deeper understanding of melanoma management, paving the way for optimized treatment strategies that improve long-term outcomes for patients.