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. 2024 Jul 17;9:175. doi: 10.1038/s41392-024-01856-7

Table 7.

Comprehensive overview of cancer therapy strategies: definitions, advantages, challenges, and comparative analysis with application examples

Treatment options Description Advantages Disadvantages Challenges Cancer Applications Examples
Small molecular inhibitor Low molecular weight compounds that target specific cellular pathways or enzymes. Simpler and less expensive synthesis and preparation processes Limited inhibitory effects on membrane proteins and secretory proteins

Challenges: Undruggable proteins

Solution: Covalent modulation, Allosteric inhibition, PROTACs, MGDs

Sotorasib: the first small molecular inhibitor targeting specific KRAS gene mutations.
Peptide drug Short chains of amino acids that mimic natural peptides or proteins, with therapeutic effects.

High efficiency at low concentrations

Strong specificity

Good safety profile

Easy synthesis

Low cost

Poor stability

Difficult oral administration

Poor membrane permeability

Enhancing stability

Facilitating oral delivery

Improving membrane permeability

Lutathera: for Gastrointestinal pancreatic neuroendocrine tumor
Monoclonal Antibody Therapy Monoclonal antibodies (mAbs) are produced by B cells and specifically target antigens.

High specificity for cancer cells

Reduced toxicity to healthy cells

Fast response and long-term immune activity

The same with the challenges.

High production costs

Antibody-related side effects

Low penetration efficiency

Long half-life with risks of adverse effects

Nivolumab: Anti PD-1 agents
Antibody drug conjugates (ADCs) Combination of a monoclonal antibody and a cytotoxic drug, targeting with precision.

Specific antigen-antibody targeting reduces systemic toxicity.

Greater design flexibility compared to conventional antibodies.

Customizable for various cancers through antigen and antibody selection.

Precise control of Drug-to-Antibody Ratio (DAR) for optimized efficacy and safety.

The same with the challenges.

Low internalization and efficiency.

Target-off toxicity.

Balancing therapeutic activity with payload toxicity.

Complex metabolism and lack of uniformity in metabolic properties.

Toxicities, including on-target/off-tumor and off-target/off-tumor effects.

Unclear mechanisms of ADC resistance.

Production and quality control difficulties.

Akalux: for head and neck cancer
Cell therapy(CAR-T as an example) A type of immunotherapy where a patient’s T cells are genetically modified to recognize and kill cancer cells.

Targeted therapy

Durability of response

Enhanced potency

Adaptive immune response

Evolution of CAR-generations

Complex manufacturing process

Toxicity and safety concerns

Limited proliferation in early generations

Need for clinical validation

solid tumor challenges

Allogeneic concerns

Challenge: Antigenic drift; System cytokine toxicities; Lack of effective targets for solid tumors; Tumor microenviroment suppression; Tumor barrier; GVHD

Solution:Tandem CAR-T; Inhibit IL-6; New tumor-specific antigens finding; co-treatment; utilize delivery routes; CD52 knockout

CD19 + CAR-T
Gene therapy(CRISPR as an example) CRISPR/Cas9 is a revolutionary gene-editing technology that allows researchers to make precise and efficient edits in the genome of cells.

Precise genome editing.

Efficient and versatile tool.

Potential for treating genetic disorders and cancer.

Enhances T cell therapies.

Aids in drug development.

Off-target effects.

Immune reactions.

Long-term efficacy.

Delivery system selection

simplicity of design

studies of longer safety in body

NCT03545815: evaluates the feasibility and safety of CRISPR-Cas9 mediated PD-1 and TCR gene-knocked out chimeric antigen receptor (CAR) T cells in phase 1 patients with mesothelin-positive multiple solid tumors
Neoantigen and cancer vaccine Vaccines designed to stimulate the immune system to recognize and attack cancer-specific neoantigens.

Effective at preventing tumor occurrence.

Potential to stimulate long-term immune memory for lasting protection against cancer recurrence.

Efficacy is inconsistent due to individual antigen variability and immune microenvironment interference.

Enhancing vaccine immunogenicity, as some patients show no response to vaccines.

Improving synthetic peptide design to increase MHC binding efficiency.

VGX-3100: a double plasmid vaccine encoding HPV protein E6 and E7.
Oncolytic virus Viruses that are genetically modified to infect, kill, and break down cancer cells directly.

Target cancer cells selectively and activate immunity.

Tumor susceptibility due to genetic defects.

Easy genome modification for targeting.

Synergy with ICIs.

limitation of targeting specificity

issue of immune response

Improve targeting specificity.

Manage immune reactions.

Optimize dosage.

Address adverse events.

T-VEC (Talimogene Laherparepvec): for melanoma, breast cancer, sarcoma, head and neck, colorectal cancer

glioma

Immunologic adjuvant and innate immunity activator Substances that enhance the body’s immune response, particularly activating the innate immune system.

Enhance vaccine effectiveness.

Reduce antigen quantities needed.

Prompt immune response to infections.

Versatile for various populations and diseases.

Potential safety and side effects.

Non-specific immune activation leading to inflammation.

Risk of resistance with prolonged use.

Unclear mechanisms in tumor environments.

Difficulties in fully understanding adjuvant mechanisms.

Toll-like receptors (TLRs) agonists
Proton therapy and carbon ion therapy High-precision radiotherapy techniques using protons or carbon ions to target tumors with minimal damage to surrounding tissue.

Precise radiation concentration on tumors.

Reduced damage to surrounding healthy tissue.

Lower adverse effects for proton therapy.

High costs and technical requirements.

Limited availability.

Debate over efficacy compared to photon therapy.

Varied efficacy and survival results for carbon-ion therapy.

Photothermal and photodynamic therapy Light-based therapies where heat (photothermal) or reactive oxygen species (photodynamic) are used to destroy cancer cells.

PTT: Minimally invasive, repeatable, no surgery needed.

PDT: High selectivity, potential immune response triggered.

Both: Limited by light penetration depth affecting large or deep tumors.

PTT: Requires strict temperature control to avoid damage.

PDT: Post-treatment photosensitivity, high costs.

GSNs
Anti-angiogenesis therapy Treatments that inhibit the formation of new blood vessels in tumors, cutting off their nutrient supply.

Inhibit tumor growth by restricting nutrient and oxygen supply.

Strong targeting with minimal impact on normal cells.

Enhance effects of other cancer treatments and delay resistance.

High costs with combination therapies.

Cardiovascular adverse reactions (e.g., hypertension, heart failure).

Primary and acquired drug resistance due to various mechanisms.

Nintedanib: a type of VEGFR-TKI
Nanomedicines Treatments that inhibit the formation of new blood vessels in tumors, cutting off their nutrient supply.

Enhanced solubility and bioavailability

Minimized off-target effects

Targeted drug delivery

Extended circulation time

Controlled release at disease site

Penetration of biological barriers

Potential toxicity

Stability and aggregation issues

Unclear body mechanisms

Unknown long-term risks

Biological complexity

Safety and biocompatibility concerns

Manufacturing scalability

Regulatory compliance

Intellectual property management

Cost-effectiveness compared to existing therapies

Iron oxide nanoparticles (such as Fe3O4 and γ-Fe2O3)
Combination therapy The use of two or more therapeutic approaches simultaneously to treat complex diseases more effectively.

Personalized treatment strategies

Potential for increased efficacy against complex diseases

FDA-approved for various cancer types

Targeted treatment for specific genetic mutations (e.g., HRR gene-mutated prostate cancer)

Strict patient selection criteria

Incompatibility and drug interactions with multiple medications

Increased frequency of adverse events (e.g., nausea, fatigue, diarrhea, vomiting, hepatic immune-related adverse events)

Critical need for precise drug selection and dosage determination

Requirement for additional animal studies and clinical trials

Urgent need for predictive biomarkers to guide treatment

Redefinition of blood test indicators for accurate treatment response assessment

Increased drug costs for patients

Atezolizumab with Bevacizumab

As more foundational research delves into the functions and mechanisms of tumors, the future of cancer treatment looks promising. In addition to the ongoing development and expansion of treatments such as ICIs, gene therapy, CAR-T, cancer vaccines, and oncolytic viruses (OVs), and the shift from traditional frontline care to combination therapies, there are several noteworthy aspects to consider for the future