The beginning of a new year traditionally invites reflection on emerging trends and future directions. Based on developments observed in 2025, we outline the most probable advances that are likely to shape clinical oncology in 2026. Rather than speculative forecasts, these perspectives reflect converging signals from clinical trials, regulatory activity, technological progress, and real-world practice.
Probability 1. Artificial intelligence will become a meaningful clinical support for patients and oncologists.
An optimistic but realistic scenario for 2026 is the widespread integration of artificial intelligence (AI) into routine oncology care as a decision-support and patient-navigation tool. AI assistants are likely to become a first point of contact for cancer patients, particularly in regions with limited access to experienced oncologists. By providing clear explanations of diagnoses, treatment options, adverse events, and prognostic expectations – delivered in the patient’s native language and adapted to local healthcare systems – AI may substantially lower barriers to timely cancer care.
Although AI will not replace oncologists from a legal or ethical standpoint, it will help close a major informational gap. Early guidance on management of adverse events (e.g., diarrhea, mucositis, fatigue) may reduce unnecessary treatment interruptions, dose reductions, and delayed referrals, ultimately improving therapeutic effectiveness.
By the end of 2026, hundreds of thousands of oncology-related patient queries are expected to further refine AI performance through continuous learning, integration with validated clinical sources, professional society guidelines, and Retrieval-Augmented Generation (RAG) frameworks. In standardized clinical scenarios such as interpretation of laboratory results or explanation of guideline-based regimens – AI already demonstrates reproducibility and consistency that in many studies meets or exceeds the average human consultation.
This is particularly relevant in oncology, where adherence to evidence-based standards directly influences outcomes. Notably, recent publications in high-impact journals illustrate AI’s potential beyond communication. In one study, an AI system analyzed over 13,000 CT scans from patients with renal tumors, generating prognostic models that outperformed traditional TNM staging and histopathologic grading in predicting relapse-free and overall survival.
As AI assumes a growing informational role, the oncologist’s function will evolve rather than diminish. The relative value of factual knowledge will decrease, while clinical judgment, ethical responsibility, empathy, and decision-making under uncertainty will become even more critical. Importantly, high-quality real-world data generated by clinicians will remain essential for training and validating AI systems, reinforcing the symbiotic relationship between human expertise and machine intelligence.
Probability 2. Molecular decision-making after surgery or radiation therapy will enter routine practice.
One of the most consequential shifts expected in 2026 is the clinical implementation of molecular tools to guide post-operative and post-radiation treatment decisions. Circulating tumor DNA (ctDNA) as a marker of minimal residual disease is transitioning from an investigational biomarker to a clinically actionable tool.
Large prospective and randomized studies in colorectal cancer (DYNAMIC, CIRCULATE-Japan, GALAXY, BESPOKE) and urothelial carcinoma (IMvigor011) have demonstrated that ctDNA enables accurate identification of patients at high risk of recurrence while safely sparing ctDNA-negative patients from unnecessary adjuvant therapy. Similar evidence is emerging for renal cell carcinoma using KIM-1 and for HPV-associated oropharyngeal cancers using circulating tumor-viral DNA.
Given the accumulating evidence and increasing regulatory acceptance, molecularly guided escalation or de-escalation of adjuvant therapy is likely to become standard practice in selected tumor types by 2026, although universal implementation across all malignancies remains unlikely in the near term.
Probability 3. Expansion of theranostics and radioligand therapies.
Rapid development of novel PET-CT tracers is expected to translate into new diagnostic applications by 2026, including tumor types where functional imaging has not been routinely used. PET-based imaging will also be increasingly employed for early assessment of systemic treatment response.
Parallel to diagnostic advances, radioligand therapy is poised for broader clinical adoption. New or expanded indications are anticipated in metastatic prostate cancer, neuroendocrine tumors, breast cancer, thyroid cancer, and gastrointestinal malignancies. Beyond established isotopes such as iodine, lutetium, and radium, ongoing trials are evaluating actinium, yttrium, rhenium, and phosphorus, potentially redefining the therapeutic landscape.
Probability 4. The future belongs to deeply personalized therapy.
An analysis of the trajectory of oncology regulatory approvals in 2025 shows a steady shift from “universal” indications to biomarker-driven strategies, including mandatory companion diagnostics, broad NGS panels, and agnostic approaches – it doesn’t matter what the tumor is, as long as its cells contain the desired drug target. We analyzed FDA approvals this year. In solid tumors, as of the time of this publication, the FDA has approved 39 original drugs/indications, half of which (18) are personalized therapies.
It should be emphasized that of the second group of drugs not classified as personalized therapies, 11 belong to various classes of immunotherapy. Consequently, “truly non-personalized” molecules were approved in only 18% of cases (7 indications). Thus, therapeutic decisions are increasingly determined not by the tumor’s organ of origin, but by its molecular profile – mutations, amplifications, receptor expression, or microenvironmental signatures.
The likelihood of this trend further accelerating in 2026 is extremely high: personalization is becoming not an optional extra, but a fundamental principle of oncology development, despite the ongoing challenges of access to testing and the interpretation of complex molecular data. New drugs are also being studied against fundamentally new targets. For example, in Russia, clinical trials are also underway with personalized therapy drugs (anti-AXL drugs, the anti-FGFR1 antibody OM-RCA-01), but they are still in the early stages.
Probability 5. Continued rapid growth of antibody-drug conjugates.
The likelihood of continued dynamic growth in the antibody-drug conjugate (ADC) sector in 2026 is estimated to be extremely high – approximately 75–90%. One of the most visible quantitative indicators of this trend is the number of clinical trials launched: according to reviews for 2024–2025, 284 clinical trials involving ADCs have been initiated globally – a record figure, demonstrating a significant acceleration in development.
For example, at the 2025 AACR-NCI-EORTC symposium, 113 Phase 1–2 clinical trials of new ADCs were presented as poster presentations. Additionally, as of October 2025, analytics platforms such as Trialtrove are recording hundreds of planned and ongoing ADC studies at various stages of development (preclinical/clinical): 812 in China and 524 in the US (according to one dataset). This concentration of projects traditionally correlates with the rapid expansion of pharmaceutical companies’ R&D portfolios.
The principle of creating and studying ADCs, honed in on early drugs such as trastuzumab deruxtecan, is being modified by the creation of new antibody carriers, new stable linkers, and variations of the payloads carried by the antibody. For example, AstraZeneca is creating ADCs loaded with multiple chemotherapy drugs (currently, only attached deruxtecan).
Therefore, our forecast for 2026: as a result, increased regulatory submissions, approvals, and indication expansions (particularly in earlier disease settings and combination regimens) are highly likely in this year.
Probability 6. Cellular technologies will continue to generate interest but will not lead to drug approval for solid tumors.
Amidst rapid progress in targeted and immunotherapy, cellular technologies are developing more cautiously: despite the impressive success of CAR-T in hematological malignancies, their use in solid tumors faces fundamental biological barriers – from the difficulty of CAR-T cell penetration into solid tumors due to the immunosuppressive microenvironment to unbridled cytokine secretion. Most developments are in the early stages of clinical trials, and the results obtained are hardly revolutionary.
Therapeutic mRNA vaccines demonstrate pronounced immune responses and good tolerability in Phase 1-2 trials. Several vaccines have entered Phase 3 (for example, the Moderna/Merck programs), but if successful, sufficient data for submitting registration dossiers will likely only be available by 2027-2029. It’s worth noting that interest in mRNA vaccines is very high – over 120 clinical trials are ongoing, and this field is supported by significant investment.
Progress in TIL and TCR therapies also demonstrates that cellular approaches are gradually finding their niches and laying the foundation for the next stage of oncology treatment evolution. In 2026, unexpected approval (as with other TILs) cannot be ruled out – for another drug based on tumor-infiltrating lymphocytes (for solid tumors) and genetically modified T cells with an artificial receptor (TCR; for hematological malignancies).
Probability 7. The search for new immunotherapy options will continue, including the use of bispecific antibodies.
It is increasingly evident that immune checkpoint inhibitors beyond the PD-1/PD-L1/CTLA-4 axis and more recently LAG-3 have struggled to deliver consistent clinical benefit. The early optimism surrounding anti-TIGIT and related targets has not yet translated into meaningful success, although definitive conclusions are premature and active investigation continues.
At the same time, the migration of established (“old-guard”) immunotherapies into earlier disease settings are expected to persist. In parallel, multiple studies are evaluating highly complex combination strategies, including regimens such as pembrolizumab plus quavonlimab, lenvatinib, and belzutifan (as in the phase 3 LITESPARK-012 study), as well as combinations incorporating costimulatory agonists, metabolic modulators, cytokines, and antibody-drug conjugates. The probability that at least some of these approaches will demonstrate clinical success by 2026 remains substantial.
Against this backdrop, bispecific antibodies that redirect activated lymphocytes toward tumor cells represent a compelling new frontier in immuno-oncology. A prominent recent example is tarlatamab, approved for the treatment of advanced small cell lung cancer, which simultaneously engages DLL3 on tumor cells and CD3 on T lymphocytes to induce targeted cytotoxicity. Several bispecific antibodies based on analogous mechanisms are already approved for lymphomas and multiple myeloma, and the likelihood of additional approvals in solid tumors by 2026 is high, given the number of ongoing phase 3 trials.
Another rapidly evolving area involves therapeutic targeting of the immunosuppressive tumor microenvironment. Notably, in 2025, the CSF-1R inhibitor imactuzumab received accelerated approval. In addition, zanzalintinib, a multikinase inhibitor targeting TYRO3, AXL, and MER, with downstream suppression of tumor-associated macrophage activity has advanced into the phase 3 STELLAR-304 study.
Probability 8. We’re betting on the approval of the first PROTAC degrader in 2026.
A PROTAC (Proteolysis-Targeting Chimera degrader) is a bifunctional chimeric molecule designed to specifically destroy a specific protein in the cell by activating the ubiquitin-proteasome degradation system. Simply put, it’s a protein killer system. One ligand of the degrader captures the desired protein, while the other ligand attracts E3 ubiquitin ligase, thereby marking the protein for disposal. This triggers the disposal system – degradation in the proteasome. Typical targeted drugs inhibit or shut down the protein, while PROTAC degraders completely remove the target protein.
In 2025, the first PROTAC degrader, vepdegestant, successfully disrupted the estrogen receptor protein on breast cancer cells in the Phase 3 VERITAC-2 trial and was submitted for full FDA approval. At least five Phase 2 studies with other degraders are listed in the clinicaltrials.gov database.
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Probability 9. Radiation therapy: Focus on personalization, precision, and intensity, regardless of stage.
In the near future, patients with metastatic disease involving multiple sites will no longer be uniformly classified as palliative. In many cases, they will instead be offered fully radical treatment strategies. Stereotactic ablative radiation therapy (SABR, also referred to as SBRT) has demonstrated the lowest toxicity among available local treatment modalities for both primary tumors and metastases, with rates of grade ≥3 toxicity below 3% in meta-analyses, while achieving high efficacy – most notably excellent local control that frequently translates into improved overall survival.
SABR is already incorporated into international clinical guidelines, and its indications are expected to expand further in 2026. This trend is supported by the large number of positive prospective studies reported in 2025, including BONEY-M, RADIOSA, SOFT, TROG 20.03 AVATAR, BRALIBREAST, and others, evaluating SABR in oligometastatic and advanced disease – not only in traditionally studied malignancies such as prostate, breast, and renal cancer, but across a wide range of tumor sites. Notably, SABR has also revived interest in preoperative radiation therapy for early-stage breast cancer, a concept that had been largely abandoned for several decades.
Currently, more than 40 clinical trials investigating SABR in oligometastatic cancer are registered on clinicaltrials.gov, with a comparable number exploring combinations of SABR and immunotherapy. At the same time, the abscopal effect (widely discussed only a few years ago) is no longer viewed as a primary therapeutic objective. Instead, increasing attention is being directed toward the so-called “badscopal effect,” characterized by disease progression following radiotherapy or combined immunoradiotherapy.
One proposed mechanism suggests that radiation induces the expression of amphiregulin (AREG), an EGFR ligand, in tumor cells, leading to cellular reprogramming toward an immunosuppressive phenotype and reduced phagocytic activity. This phenomenon, effectively the inverse of the abscopal effect, may promote the growth of distant metastases and ultimately worsen survival outcomes. Identifying such radiation-induced factors and elucidating the mechanisms underlying treatment-associated progression—many of which may be therapeutically modifiable—could enable more personalized radiation strategies and improve treatment efficacy. It is anticipated that 2026 will bring substantial advances in this area.
In contrast, multiple prospective phase 3 trials evaluating concurrent chemoimmunoradiation therapy for locally advanced tumors across various sites, including lung and cervical cancer, such as PACIFIC-2 and EA5181, have failed to demonstrate superiority over standard chemoradiation. The prevailing consensus attributes these negative results primarily to two factors: increased toxicity and attenuation of immunotherapy efficacy in the context of concurrent chemoradiation.
Radiation therapy to the primary tumor and regional lymph nodes – sites critical for the generation of tumor-specific T lymphocytes, as demonstrated in numerous preclinical studies – may impair immune priming and thereby negate the benefits of concomitant immunotherapy. Furthermore, T lymphocytes are highly radiosensitive, and daily irradiation of large tissue volumes and vascular compartments through which these cells circulate can lead to rapid lymphocyte depletion, further diminishing immunotherapeutic activity.
Consequently, the therapeutic paradigm is expected to shift toward sequential rather than concurrent treatment strategies. By 2026, the predominant focus is likely to be on induction chemoimmunotherapy followed by preoperative or definitive chemoradiotherapy for locally advanced tumors, particularly those of the lung, esophagus, and cervix.
Over the past two to three years, meaningful progress has already been achieved, with several studies including INCREASE, InTRist, MDT-Bridge, and more recently APOLO and demonstrating the feasibility and high efficacy of this approach in lung cancer. Similar positive outcomes are anticipated in other difficult-to-treat locally advanced malignancies, including esophageal and cervical cancers.
Probability 10. Renewed interest in proton therapy.
About twenty years ago, proton therapy generated extraordinary enthusiasm, including predictions that it would soon replace photon-based radiation therapy altogether. This initial excitement later subsided, and it took more than a decade for robust data from prospective comparative studies to mature, alongside the global expansion of proton therapy centers. At the ASTRO 2025 congress, results related to proton therapy were presented extensively, and clinicaltrials.gov currently lists more than 900 ongoing or completed prospective studies involving proton therapy, most frequently in combination with immune checkpoint inhibitors, both in the definitive treatment of tumors across multiple sites and in the oligometastatic setting.
At present, however, the available evidence remains highly inconsistent and does not conclusively demonstrate a clear clinical advantage of proton therapy over modern photon-based techniques; in several studies, no benefit has been observed. As a result, the question of its true added value remains unresolved, and further clarification is anticipated from upcoming studies expected to report in 2026.
Written by Ilya Tsimafeyeu,
Medical Oncologist,
Member, Editorial Board, OncoDaily
Director, Bureau for Cancer Research – BUCARE, USA/Russia
Natalia Dengina,
Radiation Oncologist,
Editor-in-Chief, RUSSCO Newspaper
Head, Department of the Radiation Therapy, Ulyanovsk Regional Cancer Center, Russia