The preceding table encapsulates seminal instances of assorted classifications of cancer vaccines, encompassing peptide-based, DNA/RNA-based, viral-vector-based, dendritic-cell-based, and whole-cell-based vaccines. Each paradigm is delineated in exhaustive detail, supplemented by pertinent bibliographical citations for subsequent scholarly inquiry.

4.6. Another Cancer Vaccine Therapy: In Situ Cancer Vaccines

In situ cancer vaccines represent a therapeutic approach where the tumor inside a patient’s body is directly targeted to serve as its own vaccine [63]. Rather than extracting tumor cells for external processing and reintroduction, in situ vaccines stimulate the immune system by damaging the tumor in its native environment [63]. As the tumor cells die, they release antigens, which are then recognized by the immune system. Often, this is achieved by injecting immune-stimulating agents or oncolytic viruses into the tumor [176,177]. This not only aims to destroy the immediate tumor but also primes the immune system to recognize and combat tumor cells elsewhere in the body [176]. In situ cancer vaccines have shown promise in preliminary studies.

4.7. Influencing Factors of Tumor Vaccines

Boosting the power of cancer vaccines is a top priority for researchers, who are diving deep into adjuvants and combination therapies to ramp up immune responses, outsmart tumor immune evasion, and prevent cancers from coming back [178,179]. The efficacy of cancer vaccines hinges on several factors, including picking the right antigens, choosing the adjuvants wisely, and using the best delivery systems [2]. Antigen selection is of paramount significance. The antigens should be specific to the tumor, or associated with it, so that the immune response zeroes in on cancer cells without harming healthy tissues [180]. Plus, the chosen antigens need to be highly immunogenic and able to stimulate both CD8+ cytotoxic T cells and CD4+ helper T cells for a strong, long-lasting attack against tumors [15]. Adjuvants help by making cancer vaccines more immunogenic. They stimulate the innate immune system, encourage antigen uptake by APCs, and help activate and expand antigen-specific T cells [181,182]. There are different types of adjuvants, like alum, toll-like receptor (TLR) agonists, and cytokines, each with unique mechanisms of action and varying effectiveness [183,184]. The latest research shows that TLR agonists, such as TLR9 and TLR7/8 agonists, have shown promise by bolstering antigen-presenting cells and intensifying immune responses [185]. Researchers have developed a nanosystem that can inhibit a process called MerTK-mediated efferocytosis. This inhibition leads to the release of immunogenic contents into the tumor microenvironment, potentially boosting the body’s natural defenses against the tumor [186]. Similarly, STING agonists enhance dendritic cell activity, boosting T-cell responses against tumors [187,188]. Oncolytic viruses, while serving as direct antitumor agents, also act as adjuvants by releasing tumor antigens within an inflammatory milieu [132]. These recent breakthroughs encapsulate the dynamic progression in adjuvant research, aiming to optimize the immune system’s potency against tumors.

5. Combination Therapies

Combining cancer vaccines with other therapies has emerged as a promising strategy to enhance the overall therapeutic efficacy and overcome the limitations of single-agent treatments [189]. Cancer vaccines, which aim to stimulate a patient’s immune system to recognize and attack tumor cells, may benefit from being combined with other immunotherapies, such as immune checkpoint inhibitors, to boost immune responses and counteract immunosuppressive mechanisms within the tumor microenvironment (TME) [190]. Several types of combination therapies involving cancer vaccines and other treatment modalities have been explored in recent years, such as combining cancer vaccines with chemotherapy, targeted therapies, and radiation therapy [189]. These combination approaches hold significant promise for optimizing cancer treatment outcomes and providing more effective, personalized therapy options for patients [74].

5.1. Cancer Vaccine + Immune Checkpoint Inhibitors

These vaccines can be combined with other treatments to enhance their effectiveness. Immune checkpoint inhibitors like pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) disable immune checkpoints, thereby unleashing a more potent attack on cancer cells [191,192,193,194]. This combination hopes to enhance recognition of cancer cells (via the vaccine) and amplify the immune response (via the checkpoint inhibitors) [5,178]. This combined approach has shown promise in preclinical models and early clinical trials by generating tumor-specific T cells and preventing their exhaustion [195]. The mechanism behind these effects is that cancer vaccines aim to boost T cells’ recognition of tumor antigens, but this immune response can be dampened by the tumor’s evasion mechanisms [196]. Enter immune checkpoint inhibitors, which block inhibitory checkpoints (PD-1 and CTLA-4) on T cells, essentially “releasing the brakes” and amplifying their antitumor activity [197]. By combining cancer vaccines, which enhance the number of tumor-recognizing T cells, with checkpoint inhibitors that ensure that these T cells are not suppressed, there is a synergistic boost in the antitumor immune response. Preliminary studies suggest that this combination augments tumor attack, potentially leading to improved patient outcomes [198,199,200,201].

5.2. Cancer Vaccine + Chemotherapy

Chemotherapy is a destructive force against cancer cells, hindering their growth and division, but may also inadvertently harm rapidly dividing normal cells such as those in bone marrow, the digestive tract, and skin [202]. The potential synergy between cancer vaccines and chemotherapy arises from some chemotherapeutic agents inducing immunogenic cell death, increasing the visibility of dying cancer cells to the immune system and potentially enhancing the efficacy of cancer vaccines [203]. Several chemotherapeutic agents have been identified to potentially enhance the efficacy of cancer vaccines due to their immunomodulatory effects. For instance, cyclophosphamide and temozolomide can deplete immune-suppressing regulatory T cells (Tregs), creating a more receptive tumor environment for vaccine action [204]. Docetaxel, used for cancers like breast and prostate cancers, can bolster antigen presentation, thereby enhancing immune recognition of tumor cells [205]. Gemcitabine targets and reduces myeloid-derived suppressor cells (MDSCs) [206]. When combined with cancer vaccines, these agents can modify the tumor environment, diminish immune suppression, or amplify the immune response against tumors, although the choice of combination depends on multiple factors, including cancer type and patient health [203]. However, there are substantial challenges to this approach. Determining the optimal timing and dosage of chemotherapy in relation to cancer vaccines remains a complex task [159]. The side effects of both chemotherapy and cancer vaccines, including chemotherapy’s often severe systemic side effects such as fatigue, infection, hair loss, and nausea, are a significant concern [207]. Furthermore, the treatment’s responsiveness is limited, as not all cancer types respond well to chemotherapy or cancer vaccines, with variability in individual patient responses adding to the complexity of treatment plans [208,209]. Additionally, the complexity of the tumor microenvironment, which can evolve various mechanisms to resist or evade treatment, may limit the effectiveness of these combined therapies [210].

5.3. Cancer Vaccine + Radiotherapy

Radiotherapy employs high-energy particles or waves, such as X-rays, gamma rays, electron beams, or protons, to annihilate or damage cancer cells. This radiation induces small breaks in the DNA inside cells, inhibiting their growth and division, and eventually leading to their death [211]. When combined with tumor vaccines, these treatments might produce a synergistic effect, with radiotherapy potentially leading to the release of cancer cell antigens and stimulating the immune system, thereby enhancing the effectiveness of cancer vaccines [212,213,214]. Research indicates that radiotherapy exerts both cytotoxic and immunomodulatory effects on the tumor microenvironment. Beyond directly damaging tumor cells, RT induces immunogenic cell death, leading to the release of damage-associated molecular patterns (DAMPs) [215]. These DAMPs serve as “danger signals”, enhancing dendritic cell function and fostering antitumor immune responses. Concurrently, radiotherapy damages the tumor vasculature, increasing its permeability due to direct effects on endothelial cells and the upregulated release of VEGF from irradiated tumor cells [215,216]. This can lead to both transient improvements in oxygen and nutrient delivery and enhanced immune cell infiltration into the tumor. However, this combination approach has its limitations. Not all patients or cancer types respond well to either radiotherapy or cancer vaccines, making the efficacy of this approach unclear in a broad population [217]. The optimal timing and dosage of radiotherapy relative to cancer vaccines are not well understood, posing a risk of radiotherapy killing immune cells stimulated by the vaccine, and thereby reducing the effectiveness of the treatment [218]. Both treatments can cause side effects, such as skin changes, fatigue, and other symptoms for radiotherapy, and usually mild but possibly flu-like symptoms for cancer vaccines [63], and some tumors may develop resistance to radiotherapy, which could limit the effectiveness of this combined approach [219].

5.4. Cancer Vaccine + Targeted Therapy

Compared to cancer vaccines, targeted therapies obstruct specific proteins or processes that aid in cancer growth and progression, offering a more cancer-cell-selective approach compared to traditional chemotherapy and resulting in fewer side effects. Notable targeted therapies include small-molecule inhibitors, like Gleevec (imatinib), and monoclonal antibodies, like Herceptin (trastuzumab) [220,221,222]. When utilized in combination, targeted therapies aim to inhibit cancer cells’ proliferation and survival, rendering the cancer cells more susceptible to the immune response provoked by the cancer vaccine. Studies have revealed the potential of this combination, with targeted therapies able to modulate the tumor microenvironment, thereby possibly enhancing the effectiveness of the vaccine-stimulated immune response [223] and helping to prevent or delay resistance to targeted therapies [2]. However, challenges and limitations remain, including the development of resistance to targeted therapies over time [224], potential side effects ranging from mild skin rashes or diarrhea to severe liver toxicity or heart problems [225], limited responsiveness in certain cancer types or patients [208], and the complex and not fully understood interaction effects between cancer vaccines and targeted therapies, which could potentially interfere with the vaccine-stimulated immune response [16].

5.5. Cancer Vaccine + Oncolytic Virotherapy

Oncolytic virotherapy constitutes a novel paradigm in the therapeutic approach towards malignant neoplasms, exhibiting a mechanism of action that distinguishes it from traditional tumor vaccines. It capitalizes on the unique capabilities of selected or genetically engineered viruses, which are orchestrated to specifically target and eradicate neoplastic cells [19,226]. Upon administration, these oncolytic viruses infiltrate the patient’s system, subjugating cancerous cells and commandeering their biological machinery for viral replication, consequently leading to cell lysis [227,228]. This lysogenic cycle not only facilitates direct oncolysis but also liberates tumor-specific antigens, providing a catalyst for the patient’s immune system to mount an anticancer response—an underpinning that is shared with the concept of tumor vaccines [132]. This dual-action mechanism that harmonizes direct cellular destruction with immune activation embodies a promising pathway in the realm of cancer therapy. The dual-action mechanism encompasses direct tumor cell lysis, releasing tumor-associated antigens, and the unveiling of damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). These elements activate both the innate and adaptive arms of the immune system, enhancing antitumor responses. As newly assembled viral entities continue their onslaught against other malignant cells, a self-propagating cycle is established. Recent advancements in this burgeoning field have entailed the exploration of diverse oncolytic virus models, such as the Parapoxvirus ovis model, known to induce an immunogenic form of cell death termed pyroptosis [229]. Scientific investigations have also scrutinized the immunostimulatory effects of these bioengineered viruses and combinational therapeutic strategies that kindle pyroptosis, consequently fostering potent antitumor activity [230,231,232]. These engineered viruses have some potential in the delivery of antitumor drugs [233]. Pioneering therapeutic strategies, such as the KISIMA/VSV-GP heterologous prime–boost methodology and the development of adenovirus-based tumor vaccines, have further emphasized the potential of oncolytic virotherapy as a formidable armament in the arsenal of cancer immunotherapy [234]. Cancer vaccines and oncolytic virotherapy offer a potential synergistic approach for cancer treatment. Cancer vaccines introduce cancer-specific antigens into the body, training the immune system to recognize and attack cells displaying these antigens [5]. Concurrently, oncolytic virotherapy uses engineered viruses that selectively infect and eliminate cancer cells, subsequently releasing tumor antigens and new viral particles that can infect nearby cancer cells, thereby stimulating an immune response [19]. In combination, the cancer vaccine’s potential enhancement of the immune response, coupled with the direct cellular damage from the oncolytic virus, could increase therapeutic effectiveness. Initial studies suggest that this combination can result in a more robust and long-lasting immune response against tumors, even potentially overcoming some immune evasion tactics employed by cancer cells [235]. Nevertheless, this approach is not without limitations. The immune system could respond to the oncolytic virus, reducing its cancer-killing effectiveness [236]. Additionally, delivering both oncolytic viruses and cancer vaccines to the tumor site, particularly in solid tumors, is challenging [237]. The diverse nature of cancers and variability in patient responses can limit the overall responsiveness of this combined therapy [238]. Finally, safety is a significant concern, as both oncolytic virotherapy and cancer vaccines can cause side effects, with the former potentially leading to severe or life-threatening reactions in rare instances [239]. Recent advancements will change this domain. Viruses are now engineered for heightened tumor specificity, some are armed with therapeutic genes to turn tumors into producers of anticancer agents, and combinations with treatments like immune checkpoint inhibitors are showing synergistic effects [240,241]. Moreover, refined genetic engineering techniques have improved the safety profiles of these oncolytic viruses, making them more amenable for therapeutic applications [242,243]. This means that they have reduced virulence in non-target tissues and minimized side effects.

6. Personalized Cancer Vaccines

Personalized cancer vaccine therapy is an innovative approach that tailors cancer treatment to a patient’s unique tumor profile. The process can be outlined as follows (Figure 4).

6.1. Tumor Sample Collection

A critical step in this process is the collection of tumor samples, which provide the essential genetic material needed to tailor the vaccine to the individual’s specific cancer [244]. The latest research advances have highlighted the importance of obtaining high-quality, well-preserved samples through minimally invasive techniques such as fine-needle aspiration or core-needle biopsy [245]. Additionally, there is a growing emphasis on collecting tumor samples at multiple timepoints throughout the course of treatment to account for the inherent heterogeneity of tumors and the potential for evolving cancer mutations [246]. The integration of these cutting-edge technologies and best practices in tumor sample collection is essential for maximizing the success of personalized cancer vaccine therapy [20].

6.2. Sequencing and Analysis

Sequencing and analysis empower researchers and clinicians to identify tumor-specific mutations and neoantigens that may function as potential therapeutic targets [20]. The development of next-generation sequencing (NGS) technologies, such as whole-exome and whole-genome sequencing, has greatly sped up the process and increased the precision of pinpointing tumor-specific mutations [177,247]. Concurrently, innovative computational approaches like machine learning algorithms and in silico prediction tools have emerged to forecast neoantigens with high immunogenicity, thereby expediting the selection of optimal vaccine candidates [244,248,249]. Moreover, incorporating multi-omics data, which include transcriptomics, proteomics, and epigenomics, offers a more comprehensive understanding of the tumor microenvironment and its influence on the effectiveness of personalized cancer vaccine therapy [250]. These advancements in sequencing and analysis have markedly improved the capacity to develop customized cancer vaccines, and they further emphasize the significance of multidisciplinary collaboration within the cancer immunotherapy field.

6.3. Neoantigen Selection

Neoantigen selection is vital for eliciting a robust and effective immune response [20,21]. Factors considered in the selection process include the binding affinity of the neoantigen to major histocompatibility complex (MHC) molecules, the immunogenicity of the epitope, and the likelihood of generating T-cell receptor (TCR) recognition [251,252]. Recent studies have also highlighted the importance of incorporating multi-omics data to ensure that the chosen neoantigens are effectively processed and presented on the cell surface [250]. By combining these innovative approaches, researchers have substantially improved the process of neoantigen selection, bolstering the potential for successful personalized cancer vaccine therapy.

6.4. Vaccine Design

Vaccine design directly influences the efficacy of the immune response against tumor cells [8]. Recent research advances have led to the development of various vaccine platforms, including peptide-based, nucleic-acid-based (DNA or RNA), viral-vector-based, and dendritic-cell-based vaccines, each with their own set of advantages and challenges [8,21,22]. The selection of appropriate adjuvants and delivery systems is essential for enhancing the immunogenicity of the vaccine and promoting the activation and expansion of tumor-specific T cells [253]. Innovative techniques such as liposomal and nanoparticle-based delivery systems have shown promise in improving vaccine stability, cellular uptake, and antigen presentation [254]. The swift pace of advancements in vaccine design methodologies, in conjunction with a burgeoning understanding of the tumor microenvironment and immune system, has notably augmented the potential of personalized cancer vaccine therapy, laying the groundwork for more effective and targeted cancer treatments.

6.5. Vaccine Production

The high quality of production in personalized cancer vaccine therapy is indispensable for ensuring the delivery of efficacious and safe treatment options to patients [22]. Noteworthy innovations in the production process encompass the incorporation of automation and process optimization to curtail the manufacturing duration and boost scalability [255]. Furthermore, the utilization of continuous manufacturing processes and the establishment of modular facilities have amplified flexibility and adaptability in vaccine production, thereby streamlining the supply chain for personalized therapies [256]. To ensure product quality, regulatory agencies have enforced good manufacturing practices (GMPs) and stringent quality control measures. The integration of advanced bioinformatics tools has also contributed to the acceleration of vaccine development and production, enabling more rapid clinical translation and patient access [110]. As the field of personalized cancer vaccine therapy continues to expand, further innovations in vaccine production technologies and processes will be vital to meeting the growing demand and ensuring the timely delivery of these tailored treatments.

6.6. Vaccine Administration

Vaccine administration directly impacts the induction of a robust immune response against tumor cells. The latest research advances have led to the exploration of various routes of administration, including subcutaneous, intradermal, intramuscular, and intranodal, with each route presenting unique benefits and challenges for different vaccine platforms [257,258]. The choice of administration route can influence the vaccine’s biodistribution, antigen presentation, and subsequent immune response [23]. Researchers are also investigating the optimal dosing and scheduling of these personalized vaccines to maximize their efficacy while minimizing potential adverse effects [21,259]. Recent studies have delved into the synergistic effects of merging personalized cancer vaccines with other immunotherapies to amplify therapeutic outcomes and surmount immune resistance [260]. As the realm of personalized cancer vaccine therapy continues to expand, a nuanced understanding of the optimal administration strategies, including route, dosage, and scheduling, will be pivotal for maximizing the therapeutic potential of these individualized treatments.

6.7. Immune Response Activation

The activation of the immune response is a central objective in personalized cancer vaccine therapy, aiming to instigate a robust and specific immune response against tumor cells expressing neoantigens. Recent research strides have provided a more comprehensive understanding of the mechanisms underpinning the activation of both innate and adaptive immune responses [20]. Personalized cancer vaccines endeavor to prime the immune system by presenting tumor-specific neoantigens to antigen-presenting cells (APCs) such as dendritic cells, which subsequently activate cytotoxic T lymphocytes (CTLs) to target and eliminate tumor cells [22,178,261]. A key facet of immune response activation lies in the optimization of vaccine design, thereby amplifying the immunogenicity of the vaccine and fostering the expansion of tumor-specific T cells [262]. Recent investigations have probed into combining personalized cancer vaccines with other immunotherapies to augment the antitumor immune response and counter the immune evasion strategies utilized by cancer cells [260]. As the realm of personalized cancer vaccine therapy progresses, a deeper comprehension of immune response activation and its modulation will be indispensable for maximizing the therapeutic potential of these tailored treatments.

6.8. Monitoring and Evaluation

Monitoring and evaluation are integral to ensuring the safety, efficacy, and optimization of these individualized treatments. Recent research breakthroughs have resulted in the development of comprehensive methodologies to assess both immune response and clinical outcomes in patients receiving personalized cancer vaccines [21,22]. Essential parameters for evaluating the immunological response include monitoring the expansion of vaccine-specific T cells, the production of cytokines, and the infiltration of immune cells into the tumor microenvironment [258]. These evaluations furnish invaluable insights into the vaccine’s capacity to activate and modulate the immune system. Clinical evaluation entails tracking objective responses, such as reduction in tumor size, progression-free survival, and overall survival, while also considering the patients’ quality of life [23,263]. As personalized cancer vaccines are often administered in combination with other immunotherapies, it is crucial to identify synergistic effects and ascertain the optimal treatment regimen [260,264]. Moreover, monitoring and evaluating safety profiles is imperative for identifying and managing potential adverse effects associated with personalized cancer vaccines, such as autoimmune reactions or systemic inflammation [109]. The ongoing refinement of monitoring and evaluation strategies will contribute to maximizing the therapeutic potential and safety of personalized cancer vaccine therapies, thereby enhancing patient outcomes.

6.9. Follow-Up, Maintenance, and Patient Education and Support

Continuous follow-up empowers healthcare professionals to monitor patients’ responses to therapy, assess potential adverse effects, and make necessary adjustments to treatment plans [21,265]. Maintenance therapy, including administering booster vaccinations or adjusting combination therapies, is pivotal for maintaining the antitumor immune response and preventing cancer recurrence [22,74]. Patient education forms a key aspect of personalized cancer vaccine therapy, as it enables patients to make informed decisions about their treatment and manage potential side effects [257]. Patients should be well informed about potential adverse effects of the treatment and the importance of promptly reporting these to their healthcare providers [109,261]. Moreover, the emotional and psychological wellbeing of patients can significantly influence their response to treatment, underscoring the need for comprehensive support systems. This may include mental health counseling, peer support groups, and resources for family members, creating an environment that nurtures the patient’s resilience and determination [266]. As personalized cancer vaccine therapy continues to progress, it is crucial to maintain an integrated approach that addresses all facets of patient care, including follow-up, maintenance, education, and support. This holistic approach can maximize the therapeutic potential of personalized cancer vaccines and lead to improved patient outcomes [267].

6.10. Data Collection and Analysis

Data collection and analysis stand as the cornerstones of personalized cancer vaccine development and evaluation. Recent strides in high-throughput sequencing technologies, computational methodologies, and bioinformatics have ushered in a new era, enabling researchers to more precisely identify and prioritize neoantigens, craft personalized vaccines, and keep track of immune responses [20,22,258]. Furthermore, the application of machine learning algorithms and artificial intelligence has emerged as a powerful tool to navigate the complexity of these data landscapes. This technology bolsters the capacity to predict the immunogenicity of neoantigens and assess the effectiveness of personalized cancer vaccines [252]. Standardized data collection and analysis protocols are paramount to ensure reproducibility, facilitate comparisons across studies, and promote the development of robust and reliable personalized cancer vaccine therapies [23].

6.11. Integration with Other Therapies

The integration of personalized cancer vaccines with other therapeutic modalities offers an intriguing avenue in the realm of cancer treatment. Recent scientific findings highlight the potential synergistic effects of marrying personalized cancer vaccines with other forms of immunotherapies. Notably, ICIs, which target immunosuppressive pathways like PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death ligand 1), and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), have shown promising results in combination with personalized cancer vaccines [109]. The rationale behind this combination is that the vaccine can stimulate a specific antitumor immune response, while ICIs can further enhance the function and persistence of tumor-specific T cells [191]. Additionally, personalized cancer vaccines can be combined with conventional therapies, such as chemotherapy and radiotherapy, to induce immunogenic cell death and release tumor-associated antigens, creating a more conducive environment for the activation of vaccine-induced immune responses [139]. Furthermore, combining personalized cancer vaccines with targeted therapies, such as kinase inhibitors or monoclonal antibodies, has shown promise in preclinical models by modulating the tumor microenvironment and improving immune cell infiltration [265,268].

6.12. Expanding Applications

The exploration of personalized cancer vaccine therapy applications continues to surge, unlocking new possibilities for cancer treatment across a diverse range of tumor types and stages. Groundbreaking studies have revealed the potential and effectiveness of tailored cancer vaccines against melanoma, glioblastoma, and non-small-cell lung cancer [22,263]. Aside from solid tumors, there is growing evidence of personalized cancer vaccines proving promising against hematological malignancies such as acute myeloid leukemia (AML) and multiple myeloma (MM) [269,270]. Furthermore, researchers are delving into the possibility of implementing personalized cancer vaccines during earlier disease stages, or as supplementary therapy after surgery or radiotherapy, with the ultimate goal of preventing relapse or disease progression [126]. As the development of personalized cancer vaccine therapy progresses, gaining a comprehensive understanding of the factors impacting vaccine effectiveness—including the tumor microenvironment, individual immune responses, and the dynamic interplay among various treatment approaches—becomes essential in extending its application scope. Unrelenting research and innovation are indispensable for harnessing the full therapeutic capacity of personalized cancer vaccines and enhancing outcomes for a wide spectrum of cancer patients. The world of clinical trials is abuzz with personalized cancer vaccines and neoantigen-targeting therapies [271,272]. Challenges exist, such as optimizing vaccine design and manufacturing, plus pinpointing the patients most likely to benefit from personalized immunotherapies [195,273]. Add in resistance mechanisms, sky-high costs, and complex production, and suddenly these groundbreaking treatments seem less accessible and affordable. So, the cancer immunotherapy research needs to zero in on resistance, refine neoantigen identification tech, and make personalized therapies more cost-effective and scalable [274]. This is where multi-omics approaches and AI come into play, helping to precisely stratify patients and craft combination therapies that boost efficacy while minimizing side effects [75]. Tackling these challenges and embracing emerging technologies will be the key to revolutionizing cancer treatment and offering new hope to countless patients.