Table 7.
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