Targeted Cancer Therapies

Targeted cancer therapies represent a major shift in oncology treatment by exploiting specific vulnerabilities within cancer cells. Rather than the broad cytotoxic effects of chemotherapy, targeted drugs interfere with key proteins that drive growth, spread, and survival of tumor cells. Combination approaches and new agents against additional targets continue to be areas of active research. This article outlines the development and current landscape of targeted cancer drugs, their mechanisms of action, clinical use, limitations, and the outlook for harnessing precision medicine to improve cancer treatment and the overcome limitations of other approaches.

Executive Summary

  • Targeted cancer therapies are a new approach to treating cancer that focuses on specific molecules involved in cancer growth. Unlike traditional chemotherapy, which affects all rapidly dividing cells, targeted therapies are designed to attack cancer cells more precisely. This approach often results in better effectiveness and fewer side effects.

  • There are several types of targeted therapies, including monoclonal antibodies, small molecule inhibitors, immunotherapy, and PARP inhibitors. Each type works differently, but they all aim to interfere with the processes that cancer cells use to grow and spread. These therapies are often tailored to a patient's specific type of cancer.

  • Trastuzumab (Herceptin) is a monoclonal antibody that targets the HER2 protein in breast cancer. It was one of the first targeted therapies and has significantly improved outcomes for patients with HER2-positive breast cancer. Trastuzumab works by binding to HER2 receptors on cancer cells, blocking their growth signals.

  • Imatinib (Gleevec) is a small molecule inhibitor used to treat chronic myeloid leukemia (CML). It targets a specific protein created by a genetic abnormality in CML cells. Imatinib was a groundbreaking drug that turned a once-fatal disease into a manageable condition for many patients.

  • Pembrolizumab (Keytruda) is an immunotherapy drug that helps the immune system fight cancer. It works by blocking a protein called PD-1, which normally prevents T cells from attacking other cells. By blocking PD-1, pembrolizumab allows T cells to recognize and attack cancer cells more effectively.

  • Olaparib (Lynparza) is a PARP inhibitor used to treat cancers with specific genetic mutations, particularly in ovarian and breast cancers. It works by preventing cancer cells from repairing their DNA, leading to their death. This drug is an example of how genetic testing can help guide cancer treatment.

  • Some other important targeted therapies include cetuximab for colorectal cancer, palbociclib for breast cancer, and vemurafenib for melanoma. Each of these drugs targets specific molecules or pathways that are crucial for the growth of particular types of cancer.

  • While targeted therapies have shown great promise, they also face challenges. Cancer cells can sometimes develop resistance to these drugs, requiring new treatment strategies. Researchers are working on ways to combine different targeted therapies or use them with other treatments to overcome resistance.

  • The development of targeted therapies has led to a more personalized approach to cancer treatment. Doctors now often test tumors for specific genetic mutations or protein expressions to determine which targeted therapy might work best. This approach, known as precision medicine, aims to give each patient the most effective treatment for their specific cancer.

  • The field of targeted cancer therapy is rapidly evolving. New areas of research include more advanced immunotherapies, cancer vaccines, and therapies that can be adjusted in real-time based on changes in the cancer. These cutting-edge approaches hold promise for even more effective and personalized cancer treatments in the future.

Targeted cancer therapies are a major advance in precision medicine for cancer treatment. Unlike traditional chemotherapy which kills all rapidly dividing cells, targeted therapies are designed to specifically block molecular drivers of cancer growth and progression.

There are several major classes of targeted therapies:

  • Monoclonal Antibodies

    These are immune system proteins engineered to bind to specific target proteins on cancer cells. Examples are trastuzumab (Herceptin) which targets the HER2 receptor in breast cancer and cetuximab (Erbitux) which blocks EGFR in colorectal cancer. Antibody drug conjugates like ado-trastuzumab emtansine (Kadcyla) also deliver chemotherapy directly to cancer cells.

  • Small Molecule Inhibitors

    These oral drugs can penetrate into cells and block signaling pathways that cancer cells hijack to grow and spread. Examples are imatinib (Gleevec) which targets the BCR-ABL fusion protein in chronic myeloid leukemia and osimertinib (Tagrisso) which inhibits mutated EGFR in lung cancer.

  • Immunotherapy

    Checkpoint inhibitor drugs block proteins on immune T-cells or cancer cells, releasing the brakes on the immune system to allow T-cells to kill cancer. Anti-PD-1 drugs like pembrolizumab (Keytruda) and anti-CTLA-4 agents like ipilimumab (Yervoy) are immunotherapies used for many advanced cancers.

  • PARP Inhibitors

    By blocking the PARP enzyme involved in DNA repair, these drugs cause cancer cell death in cancers with DNA repair defects like BRCA mutations. Olaparib (Lynparza) is the first approved PARP inhibitor.

The key advantage of targeted therapies is more selective anti-cancer effects based on the specific vulnerabilities of tumor cells. Matching the right drug to the right target protein or pathway delivers better efficacy with less toxicity compared to chemo. However, cancers can become resistant by activating alternate pathways. Combination targeted therapies and immunotherapies are newer approaches to overcome resistance.

Overall, targeted cancer therapies have transformed treatment for many cancers when given to the appropriate patient population. But more work is still needed to expand targeted options, understand and overcome resistance, and further improve outcomes.

Here are the top 10 targeted cancer therapies and their mechanisms of action:

Trastuzumab (Herceptin)

A monoclonal antibody that targets the HER2 protein. Used to treat HER2-positive breast and gastric cancers.

Olaparib (Lynparza)

A PARP inhibitor that blocks DNA repair. Used for ovarian and breast cancers with BRCA mutations.

Nivolumab (Opdivo)

A PD-1 immune checkpoint inhibitor antibody used for Hodgkin lymphoma and other cancers.

Ruxolitinib (Jakafi)

A JAK1/JAK2 inhibitor used for myelofibrosis and polycythemia vera.

Imatinib (Gleevec)

A tyrosine kinase inhibitor that targets the BCR-ABL fusion protein. Used for chronic myeloid leukemia and other cancers with that mutation.

Cetuximab (Erbitux)

A monoclonal antibody inhibitor of the epidermal growth factor receptor. Used for colorectal and head and neck cancers.

Vemurafenib (Zelboraf)

Inhibits mutated BRAF kinase found in melanoma and other cancers.

Pembrolizumab (Keytruda)

An immune checkpoint inhibitor antibody that blocks PD-1. Used for many advanced cancers like melanoma and lung cancer.

Palbociclib (Ibrance)

A CDK 4/6 inhibitor that blocks the cell cycle. Used for hormone receptor-positive breast cancer.

Alectinib (Alecensa)

An ALK inhibitor used for non-small cell lung cancer with ALK rearrangements.

History of Development:

  • 1980s - The HER2/neu oncogene was discovered by Dennis Slamon and colleagues at UCLA. They found it was amplified in about 30% of breast cancers and associated with aggressive disease.

  • 1990s - Genentech developed a monoclonal antibody targeting HER2, which became trastuzumab. Early trials showed activity in metastatic HER2+ breast cancer.

  • 1998 - Trastuzumab received FDA approval for metastatic HER2+ breast cancer in combination with chemotherapy after a landmark phase III trial showed improved response rate and survival.

  • 2005 - Four large adjuvant trials confirmed trastuzumab for 1 year after surgery reduced risk of recurrence by about 50% for early stage HER2+ breast cancer. This established 1 year of trastuzumab as standard of care.

Trastuzumab (Herceptin):

Resistance Mechanisms:

  • Signaling via alternate pathways like IGF-1R, FGFR, PI3K/Akt

  • Expression of p95HER2 - Constitutively active truncated form

  • Loss of PTEN function

  • HER2 mutations that prevent trastuzumab binding

  • Epithelial-to-mesenchymal transition (EMT)

  • Antigenic modulation - Internalization and masking of HER2 receptors

So in summary, Trastuzumab was a true breakthrough targeted therapy for breast cancer, improving outcomes for HER2+ patients. But ongoing work is still needed to enhance its efficacy and overcome resistance mechanisms.

Mechanism of Action:

  • Binds to domain IV of the HER2 receptor, preventing receptor dimerization and downstream signaling through pathways like PI3K/Akt and MAPK that drive cancer cell proliferation.

  • Activates antibody-dependent cell-mediated cytotoxicity (ADCC) - Immune cells bind to the Fc region of trastuzumab and directly induce apoptosis of HER2-overexpressing tumor cells.

  • Inhibits shedding of the extracellular domain of HER2, preventing the formation of the constitutively active p95HER2 fragment.

  • Normalizes abnormal activation of phosphatase PTEN by HER2 overexpression, leading to reduced Akt activation.

  • Disrupts angiogenesis by decreasing production of VEGF and increasing anti-angiogenic factors like PAI-1.

Current Status:

  • Remains standard of care for early and metastatic HER2+ breast cancer

  • Being tested in combinations to overcome resistance - e.g. with pertuzumab, T-DM1 conjugate

  • Biosimilars recently approved to expand access

  • Being studied for other HER2+ cancers like gastric and colorectal

Imatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) and other cancers driven by the BCR-ABL fusion protein. It was one of the first examples of molecularly-targeted precision medicine in cancer.

Imatinib (Gleevec)

History of Development:

  • 1960s - Nowell and Hungerford discover abnormal "Philadelphia chromosome" in CML cells

  • 1970s-80s - The Philadelphia chromosome is identified as a BCR-ABL gene fusion

  • 1990s - Druker and colleagues at Oregon Health & Science University develop imatinib and show dramatic activity against CML cells in clinical trials

  • 2001 - Imatinib received FDA approval for CML, inducing remissions as a single agent

Indications:

  • Approved for newly diagnosed and relapsed/refractory CML

  • Also approved for ALL with BCR-ABL fusion and GI stromal tumors (GIST) with c-Kit mutations

Side Effects:

  • Generally well tolerated, common side effects are fluid retention, muscle cramps, diarrhea

  • Can cause severe but rare side effects like congestive heart failure and liver toxicity

In summary, Imatinib revolutionized treatment of CML and demonstrated the potential of molecularly targeted therapy in cancer. Despite resistance, it remains first-line treatment and is a seminal example of precision oncology.

Mechanism of Action:

  • Imatinib is specifically designed to inhibit the tyrosine kinase activity of the BCR-ABL fusion protein which is central to CML pathogenesis

  • By blocking this constitutively active kinase, it disrupts downstream signaling pathways like Ras/Raf/MAPK and PI3K/Akt that drive abnormal cell proliferation

Formulation and Dosing:

  • Taken orally once or twice daily

  • Typical starting dose is 400 mg daily, can be increased if inadequate response

Resistance:

  • Resistance mutations in the BCR-ABL kinase domain are the main cause (e.g. T315I)

  • Next-generation TKIs like nilotinib, dasatinib, bosutinib can overcome some mutations

Pembrolizumab Pembrolizumab(Keytruda)

Pembrolizumab is a highly selective humanized monoclonal antibody used for multiple types of advanced cancers. It was the first FDA-approved anti-PD-1 checkpoint inhibitor.

History of Development:

  • 1990s - PD-1 protein discovered by Honjo and colleagues at Kyoto University

  • 2000s - Keytruda developed by Merck after nivolumab; showed antitumor activity and acceptable toxicity in early trials

  • 2014 - FDA approved pembrolizumab for advanced melanoma after it improved survival vs ipilimumab

  • Since expanded to many other cancers like NSCLC, Hodgkin lymphoma, and head and neck cancer

Indications:

  • Advanced melanoma, NSCLC, head and neck cancer, Hodgkin lymphoma, urothelial, and other cancers

  • Can be used as monotherapy or combined with chemotherapy

  • Approved for some cancers in first-line setting

Side Effects:

  • Generally better tolerated than chemotherapy, main side effects are fatigue and decreased appetite

  • Immune-related adverse effects like colitis, pneumonitis, and endocrinopathies can occur

Overall, Pembrolizumab has become a backbone therapy for many advanced cancers. It exemplifies exciting progress in immunotherapy for cancer, with ongoing trials looking to expand its utility and improve outcomes further.

Mechanism of Action:

  • Blocks the PD-1 receptor on T-cells, releasing the brakes on the immune system and enhancing T-cell activity against cancer cells

  • PD-L1 binding to PD-1 normally inhibits T-cell activation and proliferation; pembrolizumab disrupts this checkpoint pathway

  • Reinvigorated cytotoxic T-cells can recognize and kill tumor cells expressing PD-L1

Administration:

  • Given by intravenous infusion every 3 weeks

  • Dose of 200 mg or a fixed dose of 400 mg depending on cancer type

History of Development:

  • 1990s - PARP enzymes discovered to be involved in DNA repair pathways

  • 2000s - AstraZeneca develops olaparib and shows inhibition of PARP is synthetically lethal in BRCA-deficient cells

  • 2014 - Olaparib first approved by FDA for advanced ovarian cancer with BRCA mutations

  • Since expanded to 1st-line maintenance for ovarian and breast cancers

Olaparib (Lynparza)

Olaparib is an oral PARP inhibitor used for ovarian, breast, pancreatic and prostate cancers associated with defects in DNA repair, especially BRCA mutations.

Indications:

  • Maintenance treatment of recurrent ovarian cancer with BRCA mutations

  • 1st-line maintenance for advanced ovarian and breast cancers

  • Metastatic castration-resistant prostate cancer with BRCA/ATM mutations

Side Effects:

  • Most common are fatigue, nausea, vomiting, anemia

  • Can cause severe bone marrow suppression in some patients

Mechanism of Action:

  • Inhibits PARP enzymes involved in base excision repair of single strand DNA breaks

  • This results in accumulation of DNA damage, ultimately leading to cancer cell death

  • BRCA deficiencies impair double strand break repair, so there is synthetic lethality when PARP is also inhibited

In summary, Olaparib exemplifies precision medicine through a biomarker-driven approach. It has improved outcomes for patients with DNA repair deficiencies across several cancer types. Further research aims to expand PARP inhibitors to more patient populations.

Dosing and Administration:

  • Taken orally twice daily, typical dose is 300 mg tablets

  • Given until disease progression or unacceptable toxicity

Cetuximab (Erbitux)

Cetuximab is an IgG1 chimeric monoclonal antibody used to treat metastatic colorectal cancer and head and neck squamous cell carcinoma. It targets the epidermal growth factor receptor (EGFR).

History of Development:

  • 1980s - EGFR discovered to be overexpressed on many cancer cells

  • 1990s - Cetuximab developed by ImClone Systems and shows promising activity in trials

  • 2004 - FDA initially approves cetuximab for irinotecan-refractory mCRC

  • 2006 - Approved for head and neck cancer in combination with radiation

Indications:

  • Metastatic colorectal cancer expressing EGFR, often given with chemotherapy

  • Locally advanced head and neck cancer, combined with radiation

  • Not effective for cancers with KRAS/NRAS mutations

Side Effects:

  • Acne-like rash in >90% of patients

  • Infusion reactions, headaches, fatigue, diarrhea

  • Rare but severe toxicity is pulmonary fibrosis

In summary, cetuximab is a key example of targeted therapy matching the right drug to the appropriate biomarker and cancer type. It improves outcomes in EGFR-expressing mCRC and head/neck cancer without KRAS mutations.

Mechanism of Action:

  • Binds to the extracellular domain of EGFR, preventing ligand activation and dimerization

  • Inhibits downstream signaling pathways like RAS/MAPK and PI3K/Akt that promote cancer cell proliferation

  • Also induces EGFR downregulation and enables ADCC by natural killer cells

Dosing and Administration:

  • Initial 400 mg/m2 dose followed by 250 mg/m2 weekly infusion

  • Given until disease progression or excessive toxicity

History of Development:

  • 2015 - Palbociclib receives accelerated FDA approval in combination with letrozole for metastatic HR+/HER2- breast cancer, based on improved PFS in the PALOMA-1 trial.

  • 2017 - Granted regular approval after the phase 3 PALOMA-3 trial confirmed benefit with fulvestrant in metastatic setting.

  • 2019 - Approved in early stage HR+ breast cancer after the PALOMA-2 trial. Now part of standard endocrine therapy.

  • First clinically effective CDK4/6 inhibitor. Developed by Pfizer after elucidating the role of CDK4/6 in driving HR+ breast cancer.

Palbociclib (Ibrance):

Palbociclib is a first-in-class oral CDK4/6 inhibitor used to treat metastatic hormone receptor-positive (HR+)/HER2- breast cancer.

Indications:

  • HR+/HER2- metastatic breast cancer, in combination with an aromatase inhibitor or fulvestrant

  • Also approved for early stage HR+ breast cancer (in combo with standard endocrine therapy)

Side Effects:

  • Main side effects are neutropenia, infections, fatigue, nausea

  • Requires periodic blood count monitoring due to myelosuppressive effects

Mechanism of Action:

  • Selectively inhibits CDK4 and CDK6 kinases, which regulate progression through the cell cycle

  • Blocks phosphorylation of Rb protein, halting cell cycle progression from G1 into S phase

  • Cyclin D1/CDK4/6 pathway is activated by estrogen signaling in HR+ breast cancer, so palbociclib synergizes with anti-estrogens

Dosing and Administration:

  • 125 mg capsules taken orally once daily for 21 consecutive days, followed by 7 days off

  • Given continuously in 28-day cycles, until unacceptable toxicity or disease progression

In summary, palbociclib markedly changed treatment of HR+ metastatic breast cancer. It has become part of standard first-line therapy, demonstrating the success of targeting CDK4/6 as a key driver of cancer progression.

Nivolumab (Opdivo):

Nivolumab is a PD-1 immune checkpoint inhibitor antibody used to treat various advanced cancers like melanoma, NSCLC, and renal cell carcinoma. It was the second PD-1 inhibitor approved after pembrolizumab.

History of Development:

  • 2014 - Nivolumab approved for unresectable melanoma after demonstrating improved response rate and survival compared to dacarbazine in phase 3 trial.

  • 2015 - Approved for metastatic squamous NSCLC based on overall survival benefit versus docetaxel in previously treated patients.

  • Since approved for many other cancers including in combination with other immunotherapies like ipilimumab.

  • Developed by Bristol-Myers Squibb and Medarex, after the discovery of PD-1 by Honjo and colleagues in the 1990s.

Indications:

  • Advanced melanoma, NSCLC, RCC, head and neck cancer, Hodgkin lymphoma, and more either as monotherapy or combined with ipilimumab

Side Effects:

  • Generally better tolerated than chemotherapy, with fewer side effects

  • Immune-related adverse effects like colitis, hepatitis, pneumonitis can occur

Mechanism of Action:

  • Binds to PD-1 receptors on activated T-cells, blocking their interaction with PD-L1 on tumor cells

  • Releases the brakes on anti-tumor T-cell activity imposed by the PD-1/PD-L1 pathway

  • Enhances proliferation and cytotoxic function of T-cells against cancer cells

Dosing and Administration:

  • Given intravenously every 2 weeks at flat dose of 240 mg or at 3 mg/kg

  • Treatment continued until disease progression or excessive toxicity

In summary, Nivolumab has become an integral immunotherapy for multiple cancers based on efficacy and tolerable safety profile. Ongoing research is exploring optimal combinations and expanding its utility across cancer types.

History of Development:

  • 2011 - Vemurafenib receives FDA approval for BRAF V600E mutant metastatic melanoma, after phase 3 trial showed improved overall and progression-free survival.

  • 2017 - Gains approval as adjuvant therapy for stage III melanoma with BRAF mutations.

  • Developed by Plexxikon/Roche. Dramatically shrinks tumors but resistance emerges within 6-8 months, requiring combination strategies.

Vemurafenib (Zelboraf):

Vemurafenib is a kinase inhibitor targeting BRAF V600E mutations present in approximately 50% of melanomas. 

Indications:

  • Unresectable or metastatic melanoma with BRAF V600E mutation

  • Adjuvant treatment for BRAF V600E/K stage III melanoma after surgery

Side Effects:

  • Most common are arthralgia, rash, fatigue, alopecia, photosensitivity  

  • Can cause cutaneous squamous cell carcinoma, so skin exams needed

In summary, Vemurafenib represents an important shift towards targeted therapy guided by genomic profiling of tumors. But its efficacy is limited by nearly universal acquired resistance, spurring development of combination approaches.

Mechanism of Action:

  • Selectively inhibits the mutated BRAF V600E kinase which hyperactivates the MAPK pathway driving proliferation

  • Dramatically reduces tumor size by blocking MAPK signaling and inducing apoptosis in BRAF V600E melanoma

Dosing and Administration:

  • 960 mg tablet taken orally twice daily, on an empty stomach

  • Given until disease progression or unacceptable adverse effects emerge

Resistance:

  • Unfortunately resistance nearly always develops within 6-8 months

  • Mechanisms include NRAS mutations, MEK mutations, BRAF amplifications

Alectinib (Alecensa):

Alectinib is an oral ALK inhibitor approved for ALK-positive metastatic non-small cell lung cancer resistant to crizotinib. It was designed to overcome crizotinib resistance.

History of Development:

  • 2015 - FDA grants accelerated approval to alectinib for ALK+ NSCLC after progression on crizotinib, based on response rates in two small trials.

  • 2017 - Gains regular approval and expands indication to ALK+ NSCLC treatment-naïve patients based on two phase 3 trials.

  • Developed by Chugai Pharmaceuticals. Designed to inhibit ALK mutations conferring resistance to crizotinib.

Indications:

  • ALK+ NSCLC previously treated with crizotinib

  • First-line treatment of ALK+ NSCLC

Side Effects:

  • Well-tolerated compared to chemotherapy, main side effects are constipation, fatigue, peripheral edema

  • Serious adverse effects like hepatotoxicity, ILD, QT prolongation are rare

Mechanism of Action:

  • Highly selective for ALK tyrosine kinase, with less activity against wild-type EGFR

  • Inhibits ALK signaling proteins and key downstream pathways driving proliferation

  • Crosses the blood-brain barrier to limit CNS progression

Dosing and Application:

  • 600 mg taken orally twice daily with food

  • Treatment continued until progression of toxicity

In summary, Alectinib is an important treatment option for ALK+ NSCLC patients who progress on crizotinib. It demonstrates the benefit of developing second-generation targeted therapies to overcome acquired resistance.

History of Development:

  • 2011 - Ruxolitinib becomes first FDA approved JAK inhibitor for intermediate/high-risk myelofibrosis, after two pivotal phase 3 trials.

  • 2014 - Indication expands to polycythemia vera refractory to hydroxyurea, following phase 3 RESPONSE trial.

  • Developed by Incyte Corporation. Improves splenomegaly, symptoms, and quality of life but does not prolong overall survival in myelofibrosis.

Ruxolitinib (Jakafi):

Ruxolitinib is an oral JAK1/JAK2 inhibitor approved for myelofibrosis and polycythemia vera. It was the first JAK inhibitor approved for any indication.

Indications:

  • Intermediate or high-risk myelofibrosis, including primary, post-PV, and post-ET

  • Polycythemia vera who have had inadequate response to hydroxyurea

Side Effects:

  • Thrombocytopenia, anemia, neutropenia, bruising, dizziness, headache

  • Can increase risk of infections in some patients

Mechanism of Action:

  • Inhibits JAK1/JAK2 tyrosine kinases involved in JAK-STAT signaling pathway

  • Reduces dysregulated signaling causing proliferation of myeloproliferative neoplasms

  • Also downregulates inflammatory cytokines like TNF-alpha

Dosing and Application:

  • Started at 5-20 mg twice daily based on platelet counts

  • Doses titrated to efficacy and tolerability

In summary, ruxolitinib is a targeted therapy that improved constitutional symptoms and splenomegaly associated with myeloproliferative neoplasms driven by abnormal JAK-STAT signaling. It paved the way for other JAK inhibitors.

 Some cutting edge areas of development in targeted cancer therapies include:

  • Novel Immunotherapies

    There is intense focus on discovering new immunotherapy targets beyond PD-1/PD-L1. Examples include LAG-3, TIGIT, TIM-3, CD-73 inhibitors. Combinations of multiple checkpoint inhibitors are also being explored.

  • CAR T-cell Therapy

    Engineered T cells with chimeric antigen receptors (CARs) that bind tumor antigens are showing promising results in hematologic malignancies and trials in solid tumors are ongoing.

  • Bispecific Antibodies

    These dual-targeting antibodies bring T cells and cancer cells together to enhance cytotoxicity. Some like blinatumomab are approved, while many others are in development.

  • Cancer Vaccines

    Vaccines that prime the immune system against tumor antigens are being studied, such as personalized neoantigen vaccines. The HPV vaccine is an example already in use.

  • Antibody-Drug Conjugates (ADCs)

    ADCs deliver chemotherapy directly to tumor cells while reducing systemic exposure. DS-8201a, an HER2 ADC, is showing promise in breast cancer trials.

  • Targeted Radionuclide Therapy

    Molecularly targeted radiation therapy delivering radioisotopes directly to cancer cells via antibodies or small molecules. Examples are radiolabeled PSMA inhibitors in prostate cancer.

  • Combination Targeted Therapy

    Combining inhibitors of different oncogenic pathways is being tested to overcome resistance, such as BRAF/MEK inhibitor combinations in melanoma.

  • Liquid Biopsies

    Analyzing cell-free tumor DNA and exosomes in the blood to detect emerging resistance mutations and guide therapy selection in real-time.

  • The field is moving towards more personalized, combinatorial treatments. Liquid biopsies, novel immunotherapies and CAR T cells are particularly active areas of cutting edge research.