Emerging cancer therapies: CAR-T, PROTACs, and next-generation targeting

• Cancer research is rapidly shifting toward therapies that more precisely target tumor biology, immune evasion, and metabolic dependencies.
• Major areas of innovation include CAR-T cell therapy, immune checkpoint inhibitors, gene and RNA-based approaches, metabolic depletion strategies, and PROTAC-driven protein degradation.
• Despite strong scientific momentum, many of these therapies face real-world challenges related to toxicity, delivery, resistance, cost, and equitable access.

Cancer treatment has traditionally relied on surgery, chemotherapy, and radiation—approaches that have saved many lives but often lack tumor specificity and can cause significant side effects. This comprehensive review summarizes how newer therapeutic strategies are being developed to address these limitations by focusing on the underlying biology of cancer cells and their interactions with the immune system.

This is educational information, not medical advice. The review emphasizes that while many of these emerging therapies show promise in preclinical studies and early clinical trials, most are still under active investigation and are not yet broadly applicable to all patients or cancer types.

Key therapeutic directions shaping future cancer care

Immunotherapy and engineered immune cells.
Immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4 inhibitors, work by lifting immune suppression that tumors use to evade detection. These drugs have transformed treatment for several cancers, including melanoma and lung cancer, by producing durable responses in a subset of patients. CAR-T cell therapy goes further by genetically engineering a patient’s own T cells to recognize specific cancer antigens. While CAR-T has shown remarkable success in certain blood cancers, its use is limited by severe immune-related toxicities, complex manufacturing processes, and very high costs, particularly for broader application in solid tumors.

Gene and RNA-based therapies.
Gene therapy strategies aim to correct or counteract genetic abnormalities that drive cancer growth. Approaches discussed in the review include restoring tumor suppressor genes, silencing oncogenes, and increasing tumor immunogenicity. RNA-based therapies—such as siRNA, miRNA, and related technologies—allow researchers to modulate gene expression without permanently altering DNA. These approaches offer flexibility and precision but remain constrained by challenges in safely delivering genetic material to tumor cells and avoiding unintended immune responses.

Targeted therapies and antibody–drug conjugates.
Targeted therapies exploit specific molecular features of cancer cells, enabling treatment to be tailored based on biomarkers. Antibody–drug conjugates combine the targeting ability of antibodies with potent cytotoxic agents, aiming to deliver therapy directly to cancer cells while reducing systemic exposure. Although these approaches improve selectivity, tumors can still evolve resistance or lose target expression over time, limiting long-term effectiveness.

Metabolic and microenvironment-focused strategies.
Some emerging treatments target cancer metabolism rather than specific genes or proteins. Arginine-deprivation therapy, for example, exploits the dependence of certain tumors on external arginine supply. Other strategies focus on mitochondria or immune cells within the tumor microenvironment, such as neutrophils, which can support tumor growth and metastasis. These approaches highlight the growing recognition that cancer is not only a genetic disease but also a metabolic and ecological one.

PROTAC technology and enabling tools.
PROTACs represent a newer class of therapeutics designed to eliminate disease-driving proteins rather than simply inhibiting them. By tagging target proteins for degradation, PROTACs may overcome some forms of drug resistance and expand the range of actionable cancer targets. The review also highlights supporting technologies—including nanomedicine, advanced imaging analysis, and artificial intelligence—that could improve early detection, predict treatment response, and guide personalized therapy selection.

Sources

Oluwajembola AM, Zakari S, Cleanclay WD, et al. A Review of Novel Cancer Therapeutics and Current Research Trends. The Scientific World Journal. Published November 12, 2025. PMCID: PMC12629702. PMID: 41267750.