Why Human epidermal growth factor receptor 2 (HER2) is an attractive target for ADC (2023)

HER2 (Human Epidermal Growth Factor Receptor 2) is a protein that is overexpressed in certain types of cancer, including breast cancer and gastric cancer. It plays a crucial role in promoting cancer cell growth, survival, and proliferation. This overexpression of HER2 makes it an attractive target for various therapeutic approaches, including antibody-drug conjugates (ADCs).

Here are some reasons why HER2 is a good target for ADC:

  1. High expression in cancer cells: HER2 is often overexpressed in cancer cells, particularly in breast cancer. This high expression makes it a specific marker for cancer cells and allows for targeted therapy.
  2. Limited expression in normal tissues: While HER2 is expressed at low levels in normal tissues, it is significantly upregulated in cancer cells. This differential expression pattern minimizes the potential toxicity of ADCs to healthy cells and reduces off-target effects.
  3. Role in cancer progression: HER2 is involved in key signaling pathways that promote cancer cell growth, survival, and metastasis. Inhibiting HER2 signaling can disrupt these pathways and halt cancer progression.
  4. Successful targeted therapies: Targeting HER2 with monoclonal antibodies, such as trastuzumab and pertuzumab, has shown significant clinical benefit in patients with HER2-positive breast cancer. These targeted therapies have established the importance of HER2 as a viable therapeutic target.
  5. Internalization and payload delivery: When an ADC binds to HER2 on the cancer cell surface, the complex is internalized into the cell via receptor-mediated endocytosis. This internalization process allows for efficient delivery of the cytotoxic payload carried by the ADC directly to the cancer cell, enhancing its therapeutic efficacy.
  6. Synergy with chemotherapy: ADCs combine the targeted specificity of monoclonal antibodies with the potent cytotoxic effects of chemotherapy drugs. By delivering chemotherapy directly to HER2-positive cancer cells, ADCs can maximize the efficacy of the cytotoxic payload while minimizing systemic side effects.

Overall, HER2 is a promising target for ADC development due to its high expression in cancer cells, limited expression in normal tissues, and its role in promoting cancer progression. ADCs directed against HER2 offer a targeted therapeutic strategy with the potential to improve treatment outcomes for HER2-positive cancers.

What are the current HER2 targeting drugs on the market?

There are several drugs targeting HER2 that are currently available on the market for the treatment of HER2-positive cancers, particularly breast cancer. Here are some of the notable drugs:

(Video) Are You Prepared for the New Wave of ADCs in NSCLC? Targeting HER2, HER3, TROP2, and Others

Trastuzumab (Herceptin): Trastuzumab was the first HER2-targeted therapy approved by the U.S. Food and Drug Administration (FDA) in 1998 (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327515/). It is a monoclonal antibody that binds to the HER2 receptor, inhibiting its signaling and promoting immune-mediated destruction of HER2-positive cancer cells. Trastuzumab is used in the treatment of HER2-positive breast cancer, both in the early and advanced stages, as well as in metastatic gastric cancer.

Pertuzumab (Perjeta): Pertuzumab is another monoclonal antibody that targets HER2 (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827570/). It binds to a different domain of the HER2 receptor than trastuzumab, thereby inhibiting the formation of HER2 signaling complexes. Pertuzumab is often used in combination with trastuzumab and chemotherapy for the treatment of HER2-positive metastatic breast cancer and as neoadjuvant therapy for early-stage HER2-positive breast cancer.

Ado-trastuzumab emtansine (T-DM1, Kadcyla): T-DM1 is an antibody-drug conjugate that combines trastuzumab with a cytotoxic payload called emtansine (DM1) (source: https://pubmed.ncbi.nlm.nih.gov/24682654/) . The conjugate binds to HER2 on cancer cells, gets internalized, and releases DM1 to exert its cytotoxic effects. T-DM1 is used for the treatment of HER2-positive metastatic breast cancer that has progressed after prior treatment with trastuzumab and a taxane chemotherapy.

Neratinib (Nerlynx): Neratinib is a small molecule tyrosine kinase inhibitor that irreversibly binds to the intracellular domain of the HER2 receptor, preventing HER2 activation (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628314/). It is indicated for the extended adjuvant treatment of early-stage HER2-positive breast cancer after trastuzumab-based therapy.

(Video) Anti-HER2 Mechanisms of Approved HER2 Inhibitors

Lapatinib (Tykerb/Tyverb): Lapatinib is another small molecule tyrosine kinase inhibitor that targets both HER2 and EGFR (Epidermal Growth Factor Receptor) (source: https://pubmed.ncbi.nlm.nih.gov/20110044/). It inhibits the signaling pathways mediated by these receptors and is approved for use in combination with capecitabine or letrozole for the treatment of HER2-positive metastatic breast cancer.

These drugs have revolutionized the treatment of HER2-positive cancers and have significantly improved outcomes for patients with these types of tumors.

Why Linker plays a crucial role in HER2 ADC drug research

In the context of HER2-targeted drugs, such as antibody-drug conjugates (ADCs), the linker plays a crucial role in connecting the monoclonal antibody and the cytotoxic payload. The linker serves multiple purposes in HER2 drugs, including:

  1. Stability: The linker should be stable in circulation to prevent premature release of the cytotoxic payload. It needs to withstand the physiological conditions and enzymatic degradation in the bloodstream, ensuring the intact ADC reaches the tumor site.
  2. Selective release: The linker should facilitate the selective release of the cytotoxic payload inside the target cancer cells. Once the ADC binds to HER2 receptors on cancer cells, the linker needs to be cleaved or disrupted, allowing for payload release within the target cell.
  3. Internalization: The linker may have a role in promoting internalization of the ADC-HER2 complex into the cancer cell. Internalization ensures the ADC is efficiently delivered into the target cell, allowing for payload release in the intracellular environment.
  4. Payload stability and activity: The linker should maintain the stability and activity of the cytotoxic payload during circulation and release. It should protect the payload from degradation or inactivation until it reaches the intended site of action.
  5. Pharmacokinetics: The linker can influence the pharmacokinetic properties of the ADC, such as its half-life, clearance, and distribution. The choice of linker can impact the systemic exposure and tissue distribution of the ADC, which can affect its efficacy and toxicity profile.

The design and selection of the linker in HER2 drugs are critical for achieving optimal therapeutic outcomes. Various linker types, such as cleavable linkers, non-cleavable linkers, or protease-sensitive linkers, can be utilized based on the desired mechanism of payload release and the specific characteristics of the cytotoxic agent being used.

(Video) Addressing Key Targets in Advanced NSCLC: HER2-, HER3-, and TROP2-Targeted Therapies

Common linkers used in HER2 drug conjugates

The linker types used in HER2-targeted drugs, particularly antibody-drug conjugates (ADCs), can vary depending on the specific drug design and the intended mechanism of payload release. Here are some common linker types that have been used in HER2 drugs:

  1. Cleavable linkers: Cleavable linkers are designed to be sensitive to specific intracellular conditions or enzymatic activity within the cancer cell. They allow for the selective release of the cytotoxic payload once the ADC is internalized. Cleavable linkers can be designed to be sensitive to factors such as low pH, reducing conditions, or specific enzymes present in the target cell’s lysosomes or cytoplasm. Click here for a full collection of cleavable linkers.
  2. Non-cleavable linkers: Non-cleavable linkers are more stable and resistant to degradation compared to cleavable linkers. These linkers rely on other mechanisms, such as lysosomal degradation or receptor-mediated recycling, for payload release. Non-cleavable linkers are generally more stable during circulation, reducing the premature release of the payload before reaching the target cells.
  3. Protease-sensitive linkers: Some linkers are designed to be sensitive to specific proteases present in the tumor microenvironment or within the target cancer cells. These proteases can cleave the linker and release the cytotoxic payload. Protease-sensitive linkers provide an additional level of specificity by utilizing the unique protease profiles associated with the tumor cells. Click here to see a full collection of protease-sensitive linkers
  4. Self-immolative linkers: Self-immolative linkers undergo an intramolecular rearrangement upon internalization, leading to the release of the cytotoxic payload. These linkers can be designed to be triggered by various stimuli, such as pH or enzymatic activity, resulting in payload release within the target cell.

The selection of a specific linker type depends on various factors, including the desired mechanism of payload release, the stability required during circulation, and the characteristics of the cytotoxic payload being used. The goal is to achieve optimal payload release and therapeutic efficacy while minimizing off-target effects and systemic toxicity.

As one of the major linker technology companies, AxisPharm has more than 5000 high-quality bioconjugation linkers in our San Diego warehouse. Please click here to find out how our diversified linkers can meet your research needs. We also provide custom synthesis and bioconjugation services to support ADC and AOC research and development. Click here to learn how our custom linker synthesis and bioconjugation service can benefit your ADC research.

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What is the function of human epidermal growth factor receptor 2? ›

Describes cells that have a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that make too much HER2 may grow more quickly and are more likely to spread to other parts of the body.

Why is HER2 receptor important? ›

HER2 is a membrane tyrosine kinase and oncogene that is overexpressed and gene amplified in about 20% of breast cancers. When activated it provides the cell with potent proliferative and anti-apoptosis signals and it is the major driver of tumor development and progression for this subset of breast cancer.

What are the targets for ADCs? ›

3, the target antigens of the approved ADC drugs are typically specific proteins overexpressed in cancer cells, including HER2, trop2, nectin4 and EGFR in solid tumors, and CD19, CD22, CD33, CD30, BCMA and CD79b in hematological malignancies.

What type of receptor is HER2 and why is it important? ›

Human epidermal growth factor receptor-2 (HER2) is a member of the epidermal growth factor family of tyrosine kinase receptors. This family includes HER1(Erb1), HER3 ( Erb3), and HER4 (Erb4) besides HER2. HER receptors are essential for cell proliferation, differentiation, and survival.

What is human epidermal growth factor receptor 2 HER2 ]- negative? ›

In normal cells, HER2 helps control cell growth. Cancer cells that are human epidermal growth factor receptor 2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface.

What does the IGF2 receptor do? ›

The insulin-like growth factor 2 receptor (IGF2R) plays a major role in binding and regulating the circulating and tissue levels of the mitogenic peptide insulin-like growth factor 2 (IGF2).

Is HER2 a therapeutic target? ›

Anti-HER2 therapies (also called HER2 inhibitors or HER2-targeted therapies) are a class of medicines used to treat all stages of HER2-positive breast cancer, from early-stage to metastatic, as well as certain HER2-low breast cancers.

How does HER2 promote growth? ›

The HER2-HER3 heterodimer is the most potent stimulator of downstream pathways, particularly the PI3K/Akt, a master regulator of cell growth and survival. Moreover, HER2 dimerization promotes the mislocalization and rapid degradation of cell-cycle inhibitor p27Kip1 protein leading to cell-cycle progression [7, 10, 11].

What is the mechanism of HER2 signaling? ›

(A) HER2 signal transduction. Activation of the receptor tyrosine kinase occurs by homodimerization or heterodimerization with other HER family members. Activated HER2 initiates downstream signaling through the PI3K–AKT–mTOR pathway, promoting cell proliferation and survival.

What is the most successful ADC? ›

Kadcyla (ado-trastuzumab emtansine, T-DM1), a second-generation antibody-drug conjugate (ADC), is the most commercially successful ADC.

What is efficacy of ADC? ›

Clinical efficacy of ADCs is determined by fine-tuning combination of tumor antigen, targeting antibody, cytotoxic payload and conjugation strategy (a). ADC binds to tumor target cell surface antigens (b) leading to trigger a specific receptor mediated internalization (c).

Is ADC a good role to carry? ›

The professional scene

Yes ADC may be the most frustrating role in League of Legends, but it's also still the most rewarding role. If an ADC has carried a game, it is because he has played well , even if his support has pre-chewed him on the lane.

Why is HER2 positive more aggressive? ›

Sometimes, a random genetic mutation or extra copies of the gene that encodes HER2 make these cells grow even when they shouldn't. This type of cancer is called “HER2 positive.” Because it grows more quickly, it's more aggressive than other cancers.

What does HER2 receptor mean? ›

HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). This protein promotes the growth of cancer cells. In about 1 of every 5 breast cancers, the cancer cells have extra copies of the gene that makes the HER2 protein.

What is the difference between HER2 and HER2? ›

What's the Difference Between HER2-Negative and HER2-Positive Breast Cancer? HER2-positive breast cancer has unusually high levels of the protein human epidermal growth factor receptor 2. This type of cancer grows and spreads more quickly than HER2-negative breast cancer, but it's not nearly as common.

What is human epidermal growth factor 2 HER2 test? ›

(HYOO-mun eh-pih-DER-mul grothe FAK-ter reh-SEP-ter 2 …) A laboratory test that measures the amount of HER2 protein on cancer cells or how many copies of the HER2 gene are in the DNA of cancer cells. The HER2 protein helps control normal cell growth.

Does EGF bind to HER2? ›

These and other ErbB signaling modules influence angiogenesis, cell adhesion, cell motility, development, and organogenesis (43). The ligands that bind to each monomeric receptor are shown in Table 1. Notably, 7 growth factors bind to EGFR, none binds to HER2, 2 bind to HER3, and 7 bind to HER4.

Which is more aggressive HER2-negative or HER2-positive? ›

Compared with HER2-negative breast cancers, HER2-positive breast cancers tend to: Grow more quickly. Spread more easily. Return more often (called recurrence)

Is Igf2 a tumor suppressor? ›

The role of insulin-like growth factor binding protein 2 (IGFBP2) in cancer is unclear. In general, IGFBP2 is considered to be oncogenic and its expression is often observed to be elevated in cancer. However, there are a number of conflicting reports in vitro and in vivo where IGFBP2 acts in a tumor suppressor manner.

What is the difference between IGF-1 and Igf2? ›

Igf1 and Igf2 stimulate growth and development of vertebrates. In mammals, liver-derived endocrine Igf1 mediates the growth promoting effects of GH during postnatal life, whereas Igf2 stimulates placental and fetal growth and is not regulated by GH.

What is the function of IGF-1 and Igf2? ›

Studies of transgenic and knockout mice have indicated that IGF-I and IGF-II have distinct nervous system functions. Igf1 overexpressing mice have increased postnatal brain growth,37 while Igf2 overexpression appears to have no effect on brain growth.

What is the mechanism of action of HER2-targeted therapy? ›

The mechanism of its antitumor action is by binding to the ECD of the HER2 receptor, including antibody-dependent cell-mediated cytotoxicity (ADCC), blockage of ligand-independent HER2 receptor dimerization.

What drugs target HER2 receptor? ›

New anti-HER2 ADCs
Zenocutuzumab (MCLA-128) (+ trastuzumab & vinorelbine) [56]Merus N.V.II
Tucatinib (+ trastuzumab & capecitabine) [57]Seagen Inc.II R
Neratinib (+ capecitabine) [42]Puma Biotech. Inc.III R
14 more rows

What are targeted therapies for HER2 mutations? ›

Approved Indications for HER2-Targeted Therapy

Several therapies are approved for HER2-positive breast cancer in the adjuvant and metastatic setting: trastuzumab (metastatic and adjuvant), pertuzumab (metastatic and adjuvant), lapatinib (metastatic), ado-trastuzumab emtansine (metastatic), and neratinib (adjuvant).

Is HER2 a growth factor receptor? ›

This may cause cancer cells to grow more quickly and spread to other parts of the body. Checking the amount of human epidermal growth factor receptor 2 on some types of cancer cells may help plan treatment. Also called c-erbB-2, HER2, HER2/neu, and human EGF receptor 2.

Where is HER2 expressed normally? ›

HER2 is normally expressed on cell membranes of epithelial cells of several organs like the breast and the skin, as well as gastrointestinal, respiratory, reproductive, and urinary tract [17].

Where is HER2 found in the body? ›

HER2 stands for human epidermal growth factor receptor 2. It is a gene that makes a protein found on the surface of all breast cells. It is involved in normal cell growth.

Is HER2 a tumor suppressor gene? ›

In vivo studies show that these HER2/neu repressors can act therapeutically as tumor suppressor genes for tumors that overexpress HER2/neu. These preclinical studies clearly indicate that transcriptional repressors that downregulate HER2/neu can be effective regimens for cancer treatment in a gene therapy format.

What causes overexpression of HER2? ›

High levels of HER2 protein are encountered due to overexpression caused by a mutation in the HER2 gene. HER2 produced at high levels causes uncontrolled proliferation of cells.

How does trastuzumab target HER2? ›

HER2 makes the cancer cells grow and divide. Trastuzumab is a type of targeted cancer drug called a monoclonal antibody. It works by attaching to HER2 so it stops the cancer cells from growing and dividing.

How to become the best ADC? ›

6 Tips From Your Support (An ADC Guide)
  1. Let's Go for Level 2.
  2. Buy Control Wards Too.
  3. Don't Constantly Push the Minion Wave.
  4. Invest in Healing Reduction.
  5. Watch Your Positioning.
  6. Don't Randomly Use Your Dashes.
Dec 10, 2021

Who is the top ADC support? ›

4 ADC and Support Synergies to Try in LoL
  • Lucian and Nami.
  • Xayah and Rakan.
  • Twitch and Yuumi.
  • Caitlyn and Zyra.
Jan 17, 2023

Which ADC has the best scaling? ›

Might seem pedantic, but this definitely reflects reality more accurately.
  • Fantastic scaling: kog'maw, jinx, vayne, Tristana, Aphelios, Twitch.
  • Great scaling: Kai'Sa, Sivir, Ezreal, Varus, Xayah.
  • Decent scaling: Caitlyn, Ashe, Jhin.
  • Mediocre scaling: Draven, Lucian, MF.
  • Bad scaling: Kalista.
Aug 22, 2021

What are the advantages and disadvantages of ADC? ›

Low supply voltage, low power consumption, high sampling rate, circuit simplicity and easy integration on chip are main advantages. Main disadvantages are noise, low dynamic range and nonlinearity.

What is the mechanism of action of ADC? ›

Mechanism of action of ADCs

The mAb component of the ADC enables it to circulate in the bloodstream until it finds and binds to tumour-specific (or tumour-associated) cell surface antigens present on target cancer cells.

Which are the two important aspects of the ADC? ›

Two important aspects of the ADC are its sampling rate and resolution.

Is support or ADC more important? ›

Supports have so many options to decide the game state. They don't need to rely on a successful lane to gain a big advantage on the other team. ADCs, on the other hand, need to rely on strong play from both the support and the jungler in order to find ways to efficiently succeed, no matter how good you are.

Which ADC is the tankiest? ›

The Top 7 Best Tanky ADCs in League of Legends are:
  • Draven.
  • Caitlyn.
  • Kalista.
  • Nilahn.
  • Apehlios.
  • Ashe.
  • Miss Fortune.
Dec 26, 2022

What's ADC? ›

What is analog-to-digital conversion (ADC)? Analog-to-digital conversion (ADC) is an electronic process in which a continuously variable, or analog, signal is changed into a multilevel digital signal without altering its essential content.

Does HER2-positive spread faster? ›

HER2-positive breast cancer can grow and spread faster than other breast cancers because HER2 protein speeds that growth.

Is HER2-positive a risk factor? ›

Additionally, HER2 positive cancer – which makes up about 20 percent of breast cancer cases – is more likely to affect younger women. It's important to note that having one or more of these risk factors does not mean you will be diagnosed with breast cancer.

Is HER2-positive easier to treat? ›

Doctors consider HER2-positive breast cancers more aggressive, often requiring a multi-modality approach to care, including surgery, systemic therapy, and radiation therapy. Survival rates for this type of breast cancer are good, particularly when a person receives a diagnosis and starts treatment early on.

What cancers are HER2 positive? ›

Cancers that may be HER2 positive include breast, bladder, pancreatic, ovarian, and stomach cancers. Also called c-erbB-2 positive and human epidermal growth factor receptor 2 positive.

Does HER2 positive mean chemotherapy? ›

Because HER2-positive cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with chemotherapy after surgery to reduce recurrence risk.

Do all breast cancers have HER2? ›

About one out of every five breast cancer cases have too many human epidermal growth factor receptor 2 (HER2).

How many cancers are HER2 positive? ›

About 15 out of every 100 breast cancers (about 15%) are HER2 positive. Testing breast cancer cells for the HER2 protein can help to show whether targeted drugs might work. Targeted cancer drugs are treatments that change the way cells work and help the body control the growth of cancer.

Is HER2 positive always metastatic? ›

HER2-positive breast cancer is a highly heterogeneous tumor, and about 30% of patients still suffer from recurrence and metastasis after trastuzumab targeted therapy. Predicting individual prognosis is of great significance for the further development of precise therapy.

Is HER2 positive or negative better? ›

It's healthy in normal amounts, but too much may be a sign of a certain type of breast cancer. Most people with breast cancer have a normal amount of this protein, which means you are HER2-negative. But about 1 in 5 cases are HER2-positive, which means your levels are unusually high.

What is the epidermal growth factor responsible for? ›

EGF/EGFR signaling promotes embryonic development and stem cell regeneration and regulates ion transport. EGF plays pivotal role in ulcer/wound healing.

What is epidermal growth factor do? ›

(eh-pih-DER-mul grothe FAK-ter) A protein made by many cells in the body and by some types of tumors. It causes cells to grow and differentiate (become more specialized). It is a type of growth factor and a type of cytokine.

Is HER2 positive more aggressive? ›

In about 1 of every 5 breast cancers, the cancer cells have extra copies of the gene that makes the HER2 protein. HER2 -positive breast cancers tend to be more aggressive than other types of breast cancer.

Is HER2 positive easier to treat? ›

Doctors consider HER2-positive breast cancers more aggressive, often requiring a multi-modality approach to care, including surgery, systemic therapy, and radiation therapy. Survival rates for this type of breast cancer are good, particularly when a person receives a diagnosis and starts treatment early on.

Why is epidermal growth factor receptor important? ›

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal.

What is the mechanism of action of EGF? ›

Epidermal growth factor (EGF) is a single polypeptide of 53 amino acid residues which is involved in the regulation of cell proliferation. Egf exerts its effects in the target cells by binding to the plasma membrane located EGF receptor. The EGF receptor is a transmembrane protein tyrosine kinase.

How does EGF cause cell proliferation? ›

Epidermal growth factor (EGF) may bind to EGF receptor (EGFR) on cells to activate a variety of signal pathways including MAPK-Erk, PI3K-Akt, and STAT pathways. These pathways play important roles in the cell differentiation and proliferation.

Is HER2-positive always metastatic? ›

HER2-positive breast cancer is a highly heterogeneous tumor, and about 30% of patients still suffer from recurrence and metastasis after trastuzumab targeted therapy. Predicting individual prognosis is of great significance for the further development of precise therapy.

What cancers have HER2 mutations? ›

What types of cancer can have HER2 mutations? The most common cancer to have HER2 mutations is breast cancer. In fact, HER2-positive cancers make up about 20% of breast cancer cases. However, overexpressed HER2 proteins can be found in other cancers as well, including bladder, pancreatic, ovarian, and stomach cancers.

What is the role of EGF in inflammation? ›

Epidermal growth factor (EGF) suppresses inflammation and EGF receptor inhibitors increased S. aureus colonization.

How does EGF stimulate cell growth? ›

In general, binding of its ligand, epidermal growth factor (EGF), results in stimulation of the EGFR tyrosine kinase, which in turn stimulates intracellular signal transduction, enhances transcription of growth related genes, and promotes cell growth.


1. Novel Breast Cancer Therapies: Antibody-Drug Conjugates
(i3 Health)
2. Webinar: HER2-targeted therapies in CCA
(Cholangiocarcinoma Foundation)
3. Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors
(PeerView Oncology)
4. Moving Toward Expanded Precision Treatment of HER2- or HER3-Driven Breast, GI, Lung & Other Cancers
(PeerView Oncology)
5. HER2-Positive Gastrointestinal Cancers: New Evidence and Practical Guidance With Targeted Agents
(PeerView Oncology)
6. “Path to Success in HER2 Positive Breast Cancer” by Sandra M. Swain, MD, FACP, FASCO
(UH Medicine)


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